Author Report for: Soll AHContact information:Soll Andrew HVA Wadsworth Hospital Center and the School of Medicine, University of California at Los Angeles, Los Angeles, CaliforniaUSAPhone : Fax :
Chuang CN, Chen MC, Soll AH Ref: Yale J Biol Med, 67:107, 1994 : PubMed ESTHER: Chuang_1994_Yale.J.Biol.Med_67_107 PubMedSearch: Chuang 1994 Yale.J.Biol.Med 67 107 PubMedID: 7502519 Abstract Although many aspects of the regulation of acid secretion at the cellular level among different species remains controversial, certain concepts have emerged that span the differences between species, model systems and investigators. The paracrine, endocrine, neural and autocrine pathways mediate acid secretion by acting both directly on the parietal cell and indirectly via modulation of mucosal paracrine cell function. Studies with cells isolated from the acid secreting canine oxyntic mucosa indicate that gastrin and cholinergic receptors are present on parietal cells, somatostatin cells, and the histamine-enterochromaffin-like cell (ECL). Subtypes of these receptors are clearly important; the gastrin receptor on the ECL cell and parietal cell are "B" type CCK/gastrin receptors, whereas the receptor on the somatostatin cell is an A type CCK receptor. From the vantage point of studies in the canine oxyntic mucosa, the challenge is no longer to determine whether parietal, histamine or somatostatin cells have gastrin or muscarinic receptors but to establish the physiologic relevance of the specific actions (secretory, trophic or differentiative) of these receptor subtypes. Furthermore, the mechanisms integrating these paracrine, exocrine and neural elements require elucidation. Title: Multiple pathways controlling acid secretion Lloyd KC, Soll AH Ref: J Gastroenterol, 29 Suppl 7:77, 1994 : PubMed ESTHER: Lloyd_1994_J.Gastroenterol_29 Suppl 7_77 PubMedSearch: Lloyd 1994 J.Gastroenterol 29 Suppl 7 77 PubMedID: 7921159 Abstract A simple balance exists between factors that promote ulcer disease (e.g., acid and pepsin secretion) and factors that protect the stomach from ulcer disease (e.g., mucosal defense mechanisms). These factors are regulated and control the integrity of the gastric mucosa. Some of the newest discoveries in the area of regulation of acid secretion are related to the cellular localization of physiologically relevant receptors for acid secretagogues and acid inhibitors. The ability to isolate and culture histamine-containing ECL cells and somatostatin-containing "D" cells, and the ability to clone genes encoding for specific receptors has greatly enhanced our understanding of the physiological role and the regulation of various cell types within the gastric mucosa. Title: Pertussis toxin-sensitive cholinergic inhibition of somatostatin release from canine D-cells Chan CB, Soll AH Ref: American Journal of Physiology, 255:G424, 1988 : PubMed ESTHER: Chan_1988_Am.J.Physiol_255_G424 PubMedSearch: Chan 1988 Am.J.Physiol 255 G424 PubMedID: 2902802 Abstract Development of an enriched cultured cell system allowed us to investigate the mechanism of cholinergic inhibition of somatostatin release stimulated by adenosine 3',5'-cyclic monophosphate (cAMP) and Ca2+-protein kinase C-dependent pathways of cell activation. After a 24-h culture on rat tail collagen, D-cells, quantified by immunohistochemistry, were 18-fold enriched compared with unelutriated dispersed cells. Somatostatin release from cultured cells was expressed as a percent of the somatostatin released by a specific stimulus in control cells. Under basal conditions release of somatostatin was 2.3 +/- 0.6% of the total cell content. Epinephrine (1 microM) and cholecystokinin octapeptide (10 nM) increased somatostatin release to 6.98 +/- 1.25 and 10.72 +/- 1.64%, respectively. Carbachol (1 microM) completely inhibited somatostatin release stimulated by epinephrine and reduced cholecystokinin octapeptide-stimulated release to 75% of control levels. Carbachol inhibition of the response to both epinephrine and cholecystokinin octapeptide was totally prevented by 5 h of treatment of the cells with pertussis toxin (300 ng/ml). Somatostatin release in response to the diterpene forskolin (10 microM), dibutyryl cAMP (300 microM), the phorbol ester beta-phorbol 12-myristate 13-acetate (0.1 microM), and the calcium ionophore A23187 (1 microM) was also inhibited by carbachol and prevented by pertussis toxin pretreatment. The ADP-ribosylase inhibitor isonicotinamide (1 mM) selectively blocked the effect of pertussis toxin without altering other stimulatory or inhibitory responses. These data are consistent with the view that carbachol inhibits somatostatin release at guanyl nucleotide-binding protein and/or another pertussis toxin-sensitive site. Title: Role of the cholinergic nervous system in acid secretion Chan CB, Soll AH Ref: Pharmacology, 37 Suppl 1:17, 1988 : PubMed ESTHER: Chan_1988_Pharmacology_37 Suppl 1_17 PubMedSearch: Chan 1988 Pharmacology 37 Suppl 1 17 PubMedID: 2467315 Abstract Stimulation of acid secretion by muscarinic agents involves receptors with a higher apparent affinity to the M1-antagonists, pirenzepine and telenzepine, than those regulating heart rate and salivary secretion. However, the localization of the proposed M1-receptors regulating acid secretion remains unclear. Studies with parietal cells isolated from several species indicate that parietal cells have a muscarinic receptor with low affinity for the M1-antagonists. Our studies with somatostatin cells isolated from canine fundic mucosa indicates that the muscarinic receptor inhibiting somatostatin release also is of low affinity for M1-antagonists. We have found no evidence for regulation of histamine release from canine fundic mast cells, whereas there is evidence that acetylcholine induces histamine release from the enterochromaffin-like cells of the rat and rabbit fundic mucosa. Further studies will be necessary to determine which of the muscarinic receptors potentially involved in the regulation of acid secretion is responsible for the M1-behavior of this pathway. Title: Somatostatin and muscarinic inhibition of canine enteric endocrine cells: cellular mechanisms Barber DL, Gregor M, Soll AH Ref: American Journal of Physiology, 253:G684, 1987 : PubMed ESTHER: Barber_1987_Am.J.Physiol_253_G684 PubMedSearch: Barber 1987 Am.J.Physiol 253 G684 PubMedID: 2446508 Abstract Using a recently developed canine primary enteric endocrine cell culture system, we have investigated the role of adenosine 3',5'-cyclic monophosphate (cAMP) in mediating the release of neurotensin and enteroglucagon. Epinephrine-stimulated peptide release was concomitant with an increase in cAMP accumulation. Carbachol and somatostatin (SRIF) markedly inhibited the epinephrine effect on both peptide release and cAMP content. The addition of 3-isobutyl-1-methylxanthine potentiated epinephrine-stimulated peptide release without altering the relative inhibition by carbachol and SRIF, suggesting that these agents did not inhibit endocrine cell function by increasing phosphodiesterase activity. To determine the role of cAMP production in mediating inhibition of peptide release, cells were incubated with the bacterial toxin, pertussis toxin (PT). In cultures pretreated with PT, carbachol inhibition of both peptide release and cAMP accumulation was completely reversed. In contrast, SRIF inhibition of cAMP content was completely reversed after PT treatment, but inhibition of peptide release was only partially reversed. Additionally, toxin treatment only partially reversed SRIF inhibition of forskolin- and calcium ionophore-stimulated peptide release. These data suggest that muscarinic cholinergic inhibition of neurotensin and enteroglucagon release is mediated entirely through the guanine nucleotide-binding protein (Ni) or a similar toxin-sensitive, GTP-binding protein. SRIF-inhibited peptide release is mediated partially through a toxin-sensitive substrate, as evidenced by PT reversal of reduced cAMP levels. SRIF may also inhibit neurotensin and enteroglucagon release by a cAMP-independent pathway that is not coupled to Ni or a similar PT-sensitive, GTP-binding protein. Title: Review: antisecretory drugs: cellular mechanisms of action Soll AH Ref: Aliment Pharmacol Ther, 1:77, 1987 : PubMed ESTHER: Soll_1987_Aliment.Pharmacol.Ther_1_77 PubMedSearch: Soll 1987 Aliment.Pharmacol.Ther 1 77 PubMedID: 2979219 Abstract Parietal cell secretory function may be inhibited by three mechanisms. (1) Receptors for gastrin, histamine and acetylcholine are present on the canine parietal cell, and parietal cell function may be directly inhibited by specific antagonists for each of these receptors. (2) Receptor activation of parietal cell function is mediated by cyclic AMP-dependent (histamine) and calcium-dependent (cholinergic agents and gastrin) mechanisms. The antisecretory action of prostaglandins reflect interference with histamine activation of adenylate cyclase. The current generations of calcium channel blockers have only weak antisecretory actions in vivo and are unlikely to be useful in clinical practice. (3) A third mechanism of inhibition is blockade of H+/K(+)-ATPase by substituted benzimidazoles, such as omeprazole. Each of these three mechanism provides modalities of potential clinical usefulness for treating acid-peptic disease. Gastrin and acetylcholine receptors are present on other fundic cells, in addition to the parietal cell. These other cells include the somatostatin cell in the dog fundic mucosa and the histamine-containing enterochromaffin-like (ECL) cell present in the fundic mucosa of several species. The relative impact of these receptors on different cell types on the regulation of acid secretion remains uncertain, and is probably variable among different species. One gastrin receptor of considerable importance is the gastrin receptor that exerts a trophic effect on the ECL cell in the fundic mucosa. Sustained hypergastrinaemia in response to profound hypochlorhydria is associated with hyperplasia of this cell type; the elucidation of the conditions that promote this hyperplasia and the clinical consequences of this association are pressing challenges. Title: Regulation of neurotensin release from canine enteric primary cell cultures Barber DL, Buchan AM, Walsh JH, Soll AH Ref: American Journal of Physiology, 250:G385, 1986 : PubMed ESTHER: Barber_1986_Am.J.Physiol_250_G385 PubMedSearch: Barber 1986 Am.J.Physiol 250 G385 PubMedID: 2869696 Abstract A recently developed primary cell-culture system allows direct study of the cellular mechanisms regulating neurotensin secretion from intestinal mucosal cells. We now report the use of these methods to evaluate the modulation of neurotensin release by adrenergic, cholinergic, and peptidergic transmitters. Collagenase-dispersed canine ileal mucosal cells, enriched for neurotensinlike immunoreactivity (NTLI) by centrifugal elutriation, were maintained for 48 h on collagen-coated culture dishes. Epinephrine (0.01-100 microM) stimulated a dose-dependent increase increase in NTLI secretion. The NTLI response to epinephrine increase in NTLI secretion. The NTLI response to epinephrine was competitively inhibited by propranolol, producing a parallel rightward shift of the epinephrine dose-response curve. alpha-Adrenergic agonist methoxamine (10 microM) and clonidine (10 microM) did not alter basal NTLI secretion. Epinephrine stimulation was not significantly inhibited by the alpha-adrenergic antagonists prazosin (10 microM) or yohimbine (10 microM). The diterpene forskolin, an adenyl cyclase activator, increased NTLI release and had an additive effect on the response to epinephrine. In contrast to beta-adrenergic activation, carbachol and somatostatin produced a dose-dependent inhibition of epinephrine-stimulated NTLI release. At 100 microM carbachol, NTLI release was inhibited 68%, and this action was partially blocked by atropine (0.1 microM). Somatostatin (100 nM) produced a 96% inhibition that was not surmountable by 1 mM epinephrine. These data indicate that neurotensin release is stimulated by beta-adrenergic agonists and adenylate cyclase activation. Somatostatin and the muscarinic agonist carbachol directly inhibit NTLI release. Title: Release and characterization of cholecystokinin from isolated canine jejunal cells Barber DL, Walsh JH, Soll AH Ref: Gastroenterology, 91:627, 1986 : PubMed ESTHER: Barber_1986_Gastroenterology_91_627 PubMedSearch: Barber 1986 Gastroenterology 91 627 PubMedID: 3015710 Abstract We have developed an isolated intestinal cell system to study the regulation of cholecystokinin release. Enzymatically dispersed canine jejunal mucosal cells were separated by counterflow elutriation to enrich cholecystokinin content 20-fold. Release of cholecystokinin from freshly isolated cells was determined by radioimmunoassay. Elevated extracellular potassium, dibutyryl cyclic adenosine monophosphate, and the diterpene derivative forskolin each stimulated an increase in cholecystokinin release over a 60-min period compared to basal secretion. L-Tryptophan stimulated a dose-dependent and stereospecific increase in cholecystokinin. D-Tryptophan did not significantly alter basal cholecystokinin secretion. Carbachol inhibited L-tryptophan-stimulated cholecystokinin release in a dose-dependent manner. Analysis of extracts from intact jejunal mucosa by high-pressure liquid chromatography revealed three components with cholecystokinin immunoreactivity eluting in positions with cholecystokinin 8, with cholecystokinin 33/39, and after cholecystokinin 33/39. Only the two molecular forms coeluting, respectively, with cholecystokinin 8 and cholecystokinin 33/39 were present in the elutriator-enriched jejunal cells, and these two forms of cholecystokinin immunoreactivity were released from cells upon stimulation. These data suggest that L-tryptophan directly regulates the release of cholecystokinin and that membrane depolarization and intracellular generation of cyclic adenosine monophosphate may play a role in activating cholecystokinin cells. Stimulated cholecystokinin release is inhibited by the muscarinic agonist carbachol. The molecular profile of released cholecystokinin corresponded to the two molecular components, cholecystokinin 8 and cholecystokinin 33/39, contained in dispersed cells. Title: Characterization of receptors regulating secretory function in the fundic mucosa Sanders MJ, Soll AH Ref: Annual Review of Physiology, 48:89, 1986 : PubMed ESTHER: Sanders_1986_Annu.Rev.Physiol_48_89 PubMedSearch: Sanders 1986 Annu.Rev.Physiol 48 89 PubMedID: 2423027 Abstract A model for a present view of the major pathways and receptors mediating function in the canine fundic mucosa is depicted in Figure 1. Gastrin has direct actions on the parietal cell and on the somatostatin cell; action on the parietal cell, but not somatostatin cell, is potentiated by histamine. In contrast, gastrin action on the somatostatin cell is potentiated by beta-adrenergic agonists. The potency of H2 blockers against gastrin may reflect blockage by these inhibitors of the stimulatory (parietal cell), but not the inhibitory (somatostatin cell), component of gastrin action, thus shifting the balance of gastrin effects toward the inhibitory side. The profound effects of H2 antagonists on gastrin action may also reflect an effect mediated by histamine release, but this possibility awaits direct confirmation. Cholinergic pathways also have at least dual sites of action: stimulation of the parietal cell, and blockage of the release of the inhibitory transmitter somatostatin. Anticholinergic agents may therefore have a dual acid inhibitory effect by reducing direct parietal cell stimulation and enhancing somatostatin release. There is little doubt that this model will rapidly evolve, but the concept that the pathways mediating acid secretion both converge in parallel at the parietal cell, and act in series to cause the release of paracrine transmitters, is attractive and likely to persist. Title: Mechanisms of action of antisecretory drugs. Studies on isolated canine fundic mucosal cells Soll AH Ref: Scand J Gastroenterol Suppl, 125:1, 1986 : PubMed ESTHER: Soll_1986_Scand.J.Gastroenterol.Suppl_125_1 PubMedSearch: Soll 1986 Scand.J.Gastroenterol.Suppl 125 1 PubMedID: 2881344 Abstract Cellular mechanisms underlying the actions of antisecretory agents were studied with dispersed canine fundic cells; aminopyrine accumulation monitored parietal cell (PC) function. Canine PC have pharmacologically typical histamine (H) H2 and muscarinic (M) receptors. PC also have gastrin (G) receptors, which were selectively blocked by gastrin/CCK antagonists. Potentiating interactions occurred between secretagogues, one of the components of the interdependency between regulatory pathways. Prostaglandins (PG) E2 inhibited H-stimulated PC function. Treatment of PC with pertussis toxin (PT), which inactivates the inhibitory GTP-binding protein of adenylate cyclase (Gi), markedly reduced PG inhibition, indicating PG action via Gi. PC function can also be directly inhibited by H+/K+-ATPase inhibitors, such as omeprazole. When canine mucosal cells were studied, stimulatory G and inhibitory M receptors were present on fundic somatostatin (S) cells. Histamine was localized to canine fundic mast cells, which lacked G or M receptors, a conclusion that may not pertain to fundic histamine cells in other species. Nonparietal cell receptors may be important modulators of the regulation of acid secretion. Title: Prostanoid inhibition of canine parietal cells Soll AH, Chen MC, Amirian DA, Toomey M, Alvarez R Ref: American Journal of Medicine, 81:5, 1986 : PubMed ESTHER: Soll_1986_Am.J.Med_81_5 PubMedSearch: Soll 1986 Am.J.Med 81 5 PubMedID: 2428241 Abstract Cellular mechanisms underlying the anti-secretory actions of the prostaglandin E2 analogue enprostil were studied using enzyme-dispersed, elutriator-enriched canine parietal cells and the accumulation of the weak base 14C-labeled aminopyrine as a functional index. Enprostil inhibited the accumulation of aminopyrine stimulated by histamine and the phosphodiesterase inhibitor isobutylmethyl, but not by carbachol, gastrin, or dibutyryl cyclic adenosine monophosphate. Inhibition by enprostil was dose-dependent (0.1 nM to 1 microM), with maximal inhibition ranging from 65 to 95 percent. Over the same concentration range, enprostil inhibited the histamine-stimulated generation of cyclic adenosine monophosphate. This selective inhibition of histamine activation of parietal cell function was comparable to that found for prostaglandin E2. Forskolin, a diterpene that directly activates the catalytic subunit of adenylate cyclase, was also markedly inhibited by nanomolar concentrations of prostaglandin E2 and enprostil. We conclude that at least a component of the secretory inhibition by enprostil reflects direct interference with histamine stimulation of parietal cell adenylate cyclase. Title: Pirenzepine-sensitive muscarinic receptors regulate gastric somatostatin and gastrin Sue R, Toomey ML, Todisco A, Soll AH, Yamada T Ref: American Journal of Physiology, 248:G184, 1985 : PubMed ESTHER: Sue_1985_Am.J.Physiol_248_G184 PubMedSearch: Sue 1985 Am.J.Physiol 248 G184 PubMedID: 2857528 Abstract Pirenzepine, a newly described antagonist of selective muscarinic receptors (M1), has been shown to be a potent inhibitor of acid secretion. To determine whether this property of pirenzepine can be explained in part by its actions on hormones regulating acid secretion, we examined pirenzepine's effects on gastrin and somatostatinlike immunoreactivity (SLI) secretion from the isolated, perfused rat stomach. Carbachol at a dose of 10(-6) M inhibited SLI and stimulated gastrin secretion. Both atropine and pirenzepine reversed these effects in a dose-dependent fashion with D50 values of 1 X 10(-9) and 1 X 10(-7) M, respectively, against gastrin stimulation and 1 X 10(-8) and 1 X 10(-7) M, respectively, against SLI inhibition. Pirenzepine caused a progressive parallel rightward shift in the dose-response curves for SLI inhibition and gastrin stimulation by carbachol, suggesting competitive inhibition. The apparent inhibitory constant (ki) was calculated to be approximately 2 X 10(-9) M. These results indicate that gastrin and SLI release from the stomach is governed by high-affinity muscarinic receptors that are sensitive to pirenzepine. Pirenzepine's action as an acid secretory inhibitor, and possibly as an ulcer therapy drug, may be explained in part by these effects on gastric hormone regulation. Title: Fundic mucosal muscarinic receptors modulating acid-secretion Soll AH Ref: Trends in Pharmacological Sciences, Suppl:60, 1984 : PubMed ESTHER: Soll_1984_Trends.Pharmacol.Sci_Suppl_60 PubMedSearch: Soll 1984 Trends.Pharmacol.Sci Suppl 60 Title: Autonomic regulation of somatostatin release: studies with primary cultures of canine fundic mucosal cells Yamada T, Soll AH, Park J, Elashoff J Ref: American Journal of Physiology, 247:G567, 1984 : PubMed ESTHER: Yamada_1984_Am.J.Physiol_247_G567 PubMedSearch: Yamada 1984 Am.J.Physiol 247 G567 PubMedID: 6149698 Abstract Using a newly developed system for culturing canine fundic mucosal cells, we examined regulation of the secretion of somatostatinlike immunoreactivity (SLI) by cholinergic and adrenergic transmitters. Enzyme-dispersed canine fundic mucosa cells were enriched in SLI content by counterflow elutriation and cultured on collagen for 42 h. Epinephrine alone, and in combination with gastrin, stimulated SLI secretion in a dose-dependent fashion. Propranolol did not alter the response to dibutyryl cAMP or gastrin but produced a parallel, rightward shift of the epinephrine dose-response curve with the dissociation constant (Ki) determined to be 14 nM by nonlinear curve fitting. Phentolamine, an alpha-adrenergic antagonist, enhanced SLI secretion in response to epinephrine, an effect reversed by the alpha 1-agonist methoxamine but not by the alpha 2-agonist clonidine. However, neither methoxamine nor clonidine alone inhibited the response to the beta-selective adrenergic agonist isoproterenol; thus, the existence of an adrenergic alpha 1-inhibitory receptor remained uncertain. Carbachol noncompetitively inhibited SLI secretion stimulated by gastrin, epinephrine, and dibutyryl cAMP. Atropine produced a parallel rightward shift of the carbachol dose-response curve (Ki = 0.4 nM). Pirenzepine also inhibited the effects of carbachol (Ki = 35 nM). Our studies suggest that SLI-containing cells in the canine fundic mucosa possess stimulatory beta-adrenergic receptors and inhibitory muscarinic receptors. Title: Muscarinic receptors and guanylate cyclase in mammalian gastric glandular cells Culp DJ, Wolosin JM, Soll AH, Forte JG Ref: American Journal of Physiology, 245:G760, 1983 : PubMed ESTHER: Culp_1983_Am.J.Physiol_245_G760 PubMedSearch: Culp 1983 Am.J.Physiol 245 G760 PubMedID: 6140859 Abstract To investigate the involvement of guanosine 3',5'-cyclic monophosphate (cGMP) in the cholinergic activation of gastric acid and pepsinogen secretion, we studied the subcellular and cellular relation between particulate guanylate cyclase and muscarinic cholinergic receptor sites. Subcellular fractionation of homogenates from rabbit gastric glands showed that particulate guanylate cyclase and muscarinic receptors were distributed in similar patterns, which differed from the pattern found for Na+-K+-ATPase, a marker for basal-lateral plasma membranes. Assuming a basal-lateral membrane localization for particulate guanylate cyclase and cholinergic receptors, these results suggested a heterogeneity of glandular basal-lateral membranes. The distributions of these markers among fractions enriched in isolated canine parietal or chief cells were also followed. Na+-K+-ATPase correlated with parietal cell distribution (r = 0.86) and guanylate cyclase with chief cell distribution (r = 0.76). The distribution of quinuclidinyl benzilate (QNB) binding sites indicated association of muscarinic receptors with both cell types. The similar subcellular and cellular distributions of guanylate cyclase and QNB binding sites may reflect a functional relationship of these markers in muscarinic-activated pepsinogen secretion. As seen in most other tissues, gastric glandular guanylate cyclase was not stimulated by various gastric secretagogues. We found that small changes in Ca2+ concentration, within the micromolar range, can regulate glandular guanylate cyclase activity. These results are discussed in terms of the cholinergic activation of parietal and chief cell function. Title: Regulation of pepsinogen release from canine chief cells in primary monolayer culture Sanders MJ, Amirian DA, Ayalon A, Soll AH Ref: American Journal of Physiology, 245:G641, 1983 : PubMed ESTHER: Sanders_1983_Am.J.Physiol_245_G641 PubMedSearch: Sanders 1983 Am.J.Physiol 245 G641 PubMedID: 6195927 Abstract To study the regulation of pepsinogen secretion by chief cells, we have developed techniques for the isolation, enrichment, and short-term culture of chief cells from canine stomach. The fundic mucosa was enzyme dispersed and chief cells were enriched to a content of about 70% using an elutriator rotor. After 36 h in culture confluent monolayers formed that were highly enriched in chief cells. Carbachol induced a time-dependent release of pepsinogen into the medium, with about a threefold increase in pepsinogen secretion over controls found after 60 min of incubation. Carbachol stimulation of pepsinogen secretion was dose dependent, with 5 microM producing 50% of the maximal response found at a carbachol concentration of 100 microM. Atropine (100 microM) produced a rightward shift of the dose-response curve, indicating the presence of a muscarinic receptor. Dibutyryl cAMP, 8-bromo-cAMP, and forskolin also markedly stimulated pepsinogen secretion. Secretin and vasoactive intestinal peptide (VIP) stimulated pepsinogen secretion, but the response were of smaller magnitude than found with carbachol or the cAMP analogues. The phosphodiesterase inhibitor isobutylmethylxanthine also caused a small stimulation of pepsinogen secretion but did not enhance the response to secretin or VIP. These findings indicate that epithelial monolayers can spontaneously form from isolated canine chief cells and retain functional differentiation evident by a response to stimulation. Canine chief cells in culture possess muscarinic and secretin receptors and respond to cAMP. Title: Potentiating interactions of gastric stimulants on [14 C] aminopyrine accumulation by isolated canine parietal cells Soll AH Ref: Gastroenterology, 83:216, 1982 : PubMed ESTHER: Soll_1982_Gastroenterology_83_216 PubMedSearch: Soll 1982 Gastroenterology 83 216 PubMedID: 6177574 Title: Hormone regulation of parietal cell function: gastrin interaction with a specific receptor Rutten MJ, Soll AH Ref: Annals of the New York Academy of Sciences, 372:637, 1981 : PubMed ESTHER: Rutten_1981_Ann.N.Y.Acad.Sci_372_637 PubMedSearch: Rutten 1981 Ann.N.Y.Acad.Sci 372 637 PubMedID: 6280559 Title: Extracellular calcium and cholinergic stimulation of isolated canine parietal cells Soll AH Ref: J Clinical Investigation, 68:270, 1981 : PubMed ESTHER: Soll_1981_J.Clin.Invest_68_270 PubMedSearch: Soll 1981 J.Clin.Invest 68 270 PubMedID: 7251863 Abstract The role of calcium gating in cholinergic stimulation of the function of parietal cells was studied using cells isolated from canine fundic mucosa by treatment with collagenase and EDTA and enriched by velocity separation in an elutriator rotor. Monitoring the accumulation of [14C[ aminopyrine as an index of parietal cell response, stimulation by carbachol, but not by histamine, was highly dependent upon the concentration of extracellular calcium. Incubation of parietal cells in 0-.1 mM calcium, rather than the usual 1.8 mM concentration, reduced the response to 100 microM carbachol by 92 +/- 2%, whereas histamine stimulation was impaired by 28 +/- 5%. A similar reduction in extracellular calcium suppressed the response to gastrin (100 nM) by 67 +/- 7%. The impairment of cholinergic stimulation found at low extracellular calcium concentrations was rapidly reversed with the readdition of calcium. Lanthanum, which blocks calcium movement across membranes, caused a similar pattern of effects on secretagogue stimulation of aminopyrine accumulation, with 100 microM lanthanum suppressing carbachol stimulation by 83 +/- 2%. This concentration of lanthanum suppressed gastrin stimulation by 40 +/- 7% and histamine stimulation by only 12 +/- 9%. Carbachol, but not histamine nor gastrin, stimulated 45Ca++ uptake. The magnitude of carbachol-stimulated calcium uptake correlated with the parietal cell content of the fractions examined (r = 0.88), and was dose responsive over carbachol concentrations from 1 microM to 1 mM. Atropine (100 nM) caused surmountable inhibition, and these effects of carbachol and atropine on calcium uptake correlated with their effects on oxygen consumption (r = 0.93) and [14C]-aminopyrine accumulation (r = 0.90). Cells preloaded with 45Ca++ lost cellular calcium in a time-dependent fashion; however, this rate of egress was not accelerated by treatment with histamine, gastrin, or carbachol, thus failing to implicate mobilization of intracellular calcium as primary mechanism for activation of parietal cell function. These data indicate a close link between stimulation of parietal cell function and enhancement of calcium influx by cholinergic agents. Title: Pharmacology of inhibitors of parietal cell function Soll AH Ref: J Clin Gastroenterol, 3:85, 1981 : PubMed ESTHER: Soll_1981_J.Clin.Gastroenterol_3_85 PubMedSearch: Soll 1981 J.Clin.Gastroenterol 3 85 PubMedID: 6274948 Title: The interaction of stimulants on the function of isolated canine parietal cells Soll AH, Grossman MI Ref: Philos Trans R Soc Lond B Biol Sci, 296:5, 1981 : PubMed ESTHER: Soll_1981_Philos.Trans.R.Soc.Lond.B.Biol.Sci_296_5 PubMedSearch: Soll 1981 Philos.Trans.R.Soc.Lond.B.Biol.Sci 296 5 PubMedID: 6121346 Abstract With isolation, the parietal cell is removed from the effects of the many endogenous substances that may modulate its function in intact mucosa, even in the basal state. The isolated canine parietal cell responds to the major endogenous regulators of secretion: histamine, acetylcholine and gastrin. These agents act on specific receptors as evidenced by (1) the specificity of antagonist (H2 antagonists, atropine, and dibutyryl cyclic GMP respectively), (2) the binding of radiolabelled ligands, and (3) the existence of separate second messenger systems (cyclic AMP for histamine, calcium influx for acetylcholine, and an unidentified mechanism for gastrin). Potentiating interactions, which occur between histamine and acetylcholine or histamine and gastrin, do not involve extra production of second messenger. When histamine and acetylcholine are given together, the amounts of cyclic AMP generated and of calcium entering the cell are not greater than when each is acting alone. The apparent non-specific effects of inhibitors acting in vivo, such as the inhibition of all forms of stimulation by H2 antagonists, could reflect withdrawal of the potentiating action of the background histamine always present in the mucosa. Title: Effects of chemical transmitters on function of isolated canine parietal cells Soll AH, Rodrigo R, Ferrari JC Ref: Federation Proceedings, 40:2519, 1981 : PubMed ESTHER: Soll_1981_Fed.Proc_40_2519 PubMedSearch: Soll 1981 Fed.Proc 40 2519 PubMedID: 6266880 Abstract In view of the complexity of the regulation of gastric acid secretion, isolated parietal cells offer the appealing prospect of studying the receptors and mechanisms activating this cell after it has been removed from the confusing milieu of the intact mucosa. Histamine and cholinergic agents stimulate the function of canine parietal cells by interacting with typical H2 and muscarinic receptors. Gastrin produces only a small stimulation, interacting with a third, presumably specific, receptor. Combinations of histamine and carbachol and of histamine and gastrin produce potentiating interactions. When isolated parietal cells are treated with these combinations of agents, cimetidine and atropine display and apparent lack of specificity, reminiscent of that found in vivo, and probably resulting from interference with the histamine and cholinergic components of these potentiating interactions. The action of histamine, but not of carbachol or gastrin, is linked to stimulation of cyclic AMP production by parietal cells. Two potential inhibitors of acid secretion, secretin and prostaglandin E2, also stimulate cyclic AMP production, but these later effects appeared to occur largely in nonparietal cells. PGE2 however specifically inhibits histamine-stimulated parietal cell function, apparently by blocking activation of adenylate cyclase. Cholinergic action on the other hand is closely linked to enhanced influx of extracellular calcium. Title: Secretagogue stimulation of [14C]aminopyrine accumulation by isolated canine parietal cells Soll AH Ref: American Journal of Physiology, 238:G366, 1980 : PubMed ESTHER: Soll_1980_Am.J.Physiol_238_G366 PubMedSearch: Soll 1980 Am.J.Physiol 238 G366 PubMedID: 7377310 Abstract Isolated canine gastric mucosal cells accumulate [14C]aminopyrine (AP) when treated with histamine, gastrin, and carbachol. In fractions of varying parietal cell content, this accumulation of AP correlated with the parietal cell content. Cimetidine caused parallel displacement of the dose-response curve to histamine, but failed to alter the response to carbachol or gastrin. Atropine caused parallel displacement of the dose-response curve to carbachol, but failed to inhibit the response to histamine or gastrin. The dissociation constants (Kb) for cimetidine inhibition of histamine and for atropine inhibition of carbachol were found to be 1.0 micro M and 1.3 nM, respectively, values comparable to those reported for other tissues. Thus, the isolated parietal cell appears to have pharmacologically typical H2- and muscarinic receptors, with gastrin acting at a third receptor site. Isobutyl methylxanthine (IMX) and the cAMP analogues dibutyryl cAMP (DBcAMP) and 8-bromo cAMP (but not the same analogues of cGMP) also stimulated AP accumulation. Atropine failed to inhibit the responses to IMX or DBcAMP, whereas cimetidine did inhibit the response to IMX, but not to DBcAMP. Title: Specific inhibition by prostaglandins E2 and I2 of histamine-stimulated [14C]aminopyrine accumulation and cyclic adenosine monophosphate generation by isolated canine parietal cells Soll AH Ref: J Clinical Investigation, 65:1222, 1980 : PubMed ESTHER: Soll_1980_J.Clin.Invest_65_1222 PubMedSearch: Soll 1980 J.Clin.Invest 65 1222 PubMedID: 6154063 Abstract The effects of prostaglandins E2 and I2 on accumulation of [14C]aminopyrine and the generation of cyclic AMP by fractions of dispersed canine gastric mucosal cells, enriched in their content of parietal cells, have been studied. The parietal cell content of the fractions was enriched to between 43 and 70% using an elutriator rotor. The accumulation of [14C]aminopyrine was used as the index of parietal cell response to stimulation. Prostaglandin E2 (PGE2, 0.1 nM-0.1 mM) inhibited histamine stimulated aminopyrine uptake but did not block the response to carbachol, gastrin, or dibuturyl cyclic AMP. PGE2 did, however, inhibit aminopyrine uptake stimulated by carbachol and gastrin when the response to these agents was potentiated by histamine. PGE2 (0.1 NM-0.1 mM) inhibited histamine-stimulated cyclic AMP production in a dose-dependent fashion with maximal inhibition at 1 microM PGE2. Prostacyclin also inhibited both histamine-stimulated aminopyrine accumulation and histamine-stimulated cyclic AMP production. In the absence of added histamine, PGE2 in concentrations above 1 microM and prostacyclin in concentrations above 10 microM stimulated cyclic AMP production, probably by acting on the nonparietal cells as shown in previous studies. These present data are consistent with the hypothesis that prostaglandins E2 and I2 inhibit the response of isolated parietal cells to histamine by specifically blocking histamine-stimulated cyclic AMP production. Title: Hormonal control of parietal cell function Soll AH Ref: World J Surg, 3:441, 1979 : PubMed Title: Regulation of gastric acid secretion Soll AH, Walsh JH Ref: Annual Review of Physiology, 41:35, 1979 : PubMed ESTHER: Soll_1979_Annu.Rev.Physiol_41_35 PubMedSearch: Soll 1979 Annu.Rev.Physiol 41 35 PubMedID: 219762 Abstract The three stimulants of gastric acid secretion likely to have physiological roles in regulation of secretion are acetylcholine, gastrin, and histamine. Acetylcholine is released by vagal and intramucosal reflex stimulation, acting directly on the parietal cell. Gastrin is released by peptides and free amino acids in the stomach and is the only known hormonal stimulant of acid secretion. Release of gastrin by acetylcholine may occur. However, cholinergic control of gastrin release is complex since under certain conditions anticholinergic drugs may actually enhance gastrin release. Factors regulating histamine release have not been defined, but studies with H2-receptor antagonists leave little doubt that histamine has an important role in acid secretion. Studies with isolated parietal cells indicate that histamine, gastrin, and acetylcholine each appear to act at separate receptors on the parietal cell. Anticholinergic agents specifically prevent the cellular actions of acetylcholine, cimetidine specifically inhibits stimulation by histamine, and neither inhibitor blocks the small direct response to gastrin. Furthermore potentiating interactions occur between histamine, gastrin, and cholinergic agents which may account for the interdependence of secretagogue action observed in vivo. Direct potentiating interactions occur between histamine and gastrin and histamine and carbachol but not between carbachol and gastrin. However, in the presence of histamine, carbachol, and gastrin, a three-way potentiation does occur. By interfering with the potentiating interactions between stimulants, anticholinergic agents and cimetidine display an apparent cross-specificity in vitro that resembles the effects of these agents in intact mucosa. The mechanisms underlying these interactions are unknown, but the actions of histamine appear to be mediated through increased production of cyclic AMP and cyclic AMP analogs, which mimic the interactions involving histamine itself. The secondary effectors for acetylcholine and gastrin and the mechanisms for amplification of the response to combinations of stimulants remain to be elucidated. Title: Histamine and cyclic AMP in isolated canine parietal cells Soll AH, Wollin A Ref: American Journal of Physiology, 237:E444, 1979 : PubMed ESTHER: Soll_1979_Am.J.Physiol_237_E444 PubMedSearch: Soll 1979 Am.J.Physiol 237 E444 PubMedID: 91322 Abstract The relationship between cyclic AMP production and the response of isolated canine parietal cells to histamine has been examined. Histamine increased cyclic AMP generation, and this effect correlated with histamine stimulation of oxygen consumption and aminopyrine accumulation. Metiamide inhibited histamine-stimulated cyclic AMP generation and oxygen consumption in a parallel fashion. At concentrations below 100 microM, isobutyl AMP production and oxygen consumption in a similar fashion. However, with IMX above 100 microM, histamine caused no further increases in oxygen consumption, despite markedly enhanced cyclic AMP generation. Neither carbachol nor gastrin increased cyclic AMP production beyond that produced by IMX alone, and the combinations of histamine and carbachol and of histamine and gastrin produced no greater cyclic AMP generation than produced by histamine. These findings support a close relationship between cyclic AMP production and the action of histamine but not of carbachol or gastrin on isolated parietal cells. The mechanisms underlying the potentiating interactions between histamine, carbachol, and gastrin involve step(s) beyond stimulation of cyclic AMP generation. Title: The actions of secretagogues on oxygen uptake by isolated mammalian parietal cells Soll AH Ref: J Clinical Investigation, 61:370, 1978 : PubMed ESTHER: Soll_1978_J.Clin.Invest_61_370 PubMedSearch: Soll 1978 J.Clin.Invest 61 370 PubMedID: 621277 Abstract The action of histamine, carbamylcholine, and gastrin on oxygen uptake by cells isolated from canine fundic mucosa was studied in vitro. Viable mucosal cells were prepared by exposure of separated mucosa sequentially to collagenase and EDTA. Oxygen consumption, determined by polarography, was chosen as an index of physiological response of mucosal cells to secretagogues. Isobutyl methyl xanthine (IMX), carbamylcholine, histamine, and gastrin each independently stimulated oxygen uptake by the unfractionated mucosal cells. The response to histamine was greatly enhanced when IMX was present. In fractions of varying parietal cell content obtained with the Beckman elutriator rotor, basal and stimulated oxygen uptake correlated with the parietal cell content of the fractions. The percentage increases in oxygen uptake in response to histamine, gastrin, carbamylcholine, and IMX were similar in enriched fractions with from 50 to 85% parietal cells and in unenriched starting fractions. The normalized dose-response relations for histamine with an IMX background and for carbamylcholine were also similar in these two fractions.The specificity of these responses was tested by use of an H(2)-histamine receptor antagonist, metiamide, and an anticholinergic agent, atropine. At the doses used, neither metiamide (0.1 mM) nor atropine (10 muM) inhibited basal oxygen uptake. Histamine, studied with an IMX background, was inhibited by metiamide but not by atropine, while carbamylcholine was inhibited by atropine but not by metiamide. Neither metiamide nor atropine inhibited gastrin-stimulated oxygen uptake. These data indicate that in this in vitro system parietal cells account for most of the increase in oxygen uptake produced by exposure to gastric secretagogues and that histamine, gastrin, and carbamylcholine each independently stimulate oxygen uptake by the parietal cell. The specificity displayed by atropine and metiamide in this in vitro system suggests that the parietal cell has specific receptors for each of these secretagogues. Title: The interaction of histamine with gastrin and carbamylcholine on oxygen uptake by isolated mammalian parietal cells Soll AH Ref: J Clinical Investigation, 61:381, 1978 : PubMed ESTHER: Soll_1978_J.Clin.Invest_61_381 PubMedSearch: Soll 1978 J.Clin.Invest 61 381 PubMedID: 621278 Abstract Using oxygen uptake as an index of the physiological response of isolated parietal cells, the interactions between histamine and gastrin and between histamine and carbamylcholine and the effects of atropine and metiamide on these interactions have been studied. Parietal cells were isolated from canine fundic mucosa by sequential exposure of separated mucosa to collagenase and EDTA. In previous studies carbamylcholine, isobutyl methyl xanthine, gastrin, and histamine have each been shown to increase oxygen uptake by these cells. Isobutyl methyl xanthine greatly enhanced the histamine effect. Carbamylcholine was inhibited by atropine but not by metiamide, histamine was inhibited by metiamide but not by atropine, and gastrin was inhibited by neither, suggesting that each of these agents has a direct action on the parietal cell. In the present studies, potentiating interactions between histamine and carbamylcholine and between histamine and gastrin have been demonstrated. Against a histamine (0.1 and 1 muM) plus isobutyl methyl xanthine (0.1 mM) background, the dose for 50% response for gastrin was approximately 1 nM, and the maximal response was obtained at 0.1 muM. When added to these combinations of stimulants, metiamide and atropine retained their respective specificities against stimulation by histamine and carbamylcholine, in that responses were inhibited to the level that was seen when the component of the pair that was not inhibited was given alone. The observation that histamine plus gastrin and histamine plus carbamylcholine produced maximal responses that were greater than the maximal response to histamine alone further supports the hypothesis that these agents each have direct actions on parietal cells. These observations are not consistent with the hypothesis that histamine is the sole mediator for the effects of other secretagogues. Furthermore, the inhibitory effects of atropine and metiamide on the specific cholinergic and histaminic components of the interactions that occur between secretagogues provide a possible explanation for the apparent lack of specificity of these agents on in vivo acid secretion. Title: Cellular mechanisms in acid secretion Soll AH, Grossman MI Ref: Annu Rev Med, 29:495, 1978 : PubMed Title: Studies on the actions and interactions of secretagogues on isolated mammalian parietal cells as reflected in changes in oxygen consumption and aminopyrine uptake Soll AH Ref: Gastroenterology, 73:899, 1977 : PubMed ESTHER: Soll_1977_Gastroenterology_73_899 PubMedSearch: Soll 1977 Gastroenterology 73 899 PubMedID: 902956 | |||||||
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