Hemedah_1997_J.Pharm.Pharmacol_49_1217

The effects of histamine and N(alpha)-methylhistamine, two components of gastric juice, on vagal and transmural stimulation of the guinea-pig isolated oesophagus were compared with their effects on cholinergic and on non-adrenergic-non-cholinergic (NANC) neuronal responses in the isolated ileum, both tissues having been pretreated with mepyramine (1 microM). Histamine (< or = 10 microM) and N(alpha)-methylhistamine (< or = 1 microM) had no significant effect on either vagal or transmural stimulation in the oesophagus. Substance P, which produces a contraction by activation of cholinergic nerves in the oesophagus also was unaffected by histamine. In contrast, the agonists inhibited contractions produced by cholinergic nerve stimulation in the ileum; the inhibition produced by histamine (10 microM) was up to 73 +/- 5%, that by N(alpha)-methylhistamine (1 microM), 48 +/- 5%. Histamine also inhibited responses to stimulation of NANC neurons by up to 37 +/- 14%. The effects of histamine and N(alpha)-methylhistamine in the ileum were inhibited by clobenpropit (0.1 microM). These findings suggest that histamine and N(alpha)-methylhistamine have no role in the modulation of neuronal function in the oesophagus, in contrast with their effect in the ileum.