Torocsik_1991_Eur.J.Pharmacol_202_297

The effects of nicotine and dimethylphenylpiperazinium (DMPP) on resting and stimulation-evoked release of [3H]-acetylcholine ([3H]ACh) from cholinergic interneurons and neuro-effector neurons of the ileal longitudinal muscle and the responses of the smooth muscle to nicotinic agonists were studied. (-)-Nicotine was 15 times more effective than (+)-nicotine in releasing ACh. Since tetrodotoxin (1 microM) completely antagonized the effect of nicotinic agonists, the site of action of the nicotinic agonists studied was on the somatodendritic nicotinic receptors. The electrical field stimulation-evoked release was not affected by nicotinic agonists and antagonists, indicating that the axon terminals of cholinergic interneurons are not equipped with nicotinic receptors. This preparation proved to be useful to study the effect of nicotinic agonists on somatodendritic receptors, to determine the affinity constants of nicotinic antagonists, and to characterize these receptors. The rank order of antagonists was d-tubocurarine = mecamylamine greater than pipecuronium greater than pancuronium greater than vecuronium greater than hexamethonium; the apparent affinity constants (KD) were 1.15, 1.55, 3.06, 3.98, 13.59 and 32.88 microM, respectively. alpha-Bungarotoxin had no antagonistic activity at all. This finding indicates that nicotine and the endogenous ligand ACh act via a postsynaptic, somatodendritic nicotinic receptor that is pharmacologically similar to those located on the axon terminals of sympathetic neurons or in ganglions, but is dissimilar to those located at the postsynaptic site of the neuromuscular junction.