Acetylcholine release from guinea‐pig ileum by parasympathetic ganglion stimulants and gastrin‐like polypeptides

Abstract

The release of acetylcholine by parasympathetic ganglion stimulants from the nerve terminals of the guinea‐pig longitudinal muscle strip was studied. The acetylcholine released was collected in the presence of physostigmine sulphate. Nicotine and 1,1‐dimethyl‐4′‐phenylpiperazinium iodide (DMPP) released acetylcholine. Tetrodotoxin (50 ng/ml) and hexamethonium completely prevented their action on acetylcholine release, indicating that their effect is on nicotinic receptors of cell bodies. Noradrenaline (1 μg/ml), excess magnesium, and calcium withdrawal inhibited the acetylcholine release induced by nicotine or by DMPP. There was rapid tachyphylaxis to the acetylcholine releasing action of both nicotine and DMPP. The octapeptide amide of cholecystokinin and caerulein (10−9M) enhanced the acetylcholine release without producing tachyphylaxis. Tetrodotoxin completely inhibited acetylcholine release. However, hexamethonium or desensitization with 5‐hydroxytryptamine did not prevent their action. In the early phase of nicotine action the polypeptides studied failed to increase acetylcholine release. However, a few minutes later the tissue became sensitive to polypeptides despite the fact that the tissue was still exposed to nicotine. These data suggest the presence in the parasympathetic ganglion cells of separate gastrointestinal hormone‐sensitive receptors. Noradrenaline inhibited the acetylcholine releasing action of polypeptides. This effect was mediated via α‐adrenoceptors since phentolamine prevented its action. Excess magnesium (9·3 mm) also reduced the acetylcholine release in response to the polypeptides. 1973 British Pharmacological Society