Characterization of nicotinic acetylcholine receptor-mediated noradrenaline release from the isolated rat stomach

We characterized nicotinic acetylcholine receptor-mediated noradrenaline re lease from the isolated vascularly perfused rat stomach. The stomach was pe rfused via the coeliac artery with Krebs-Ringer solution at a constant flow rate of 4 ml per minute. Endogenous noradrenaline released into the perfus ate was electrochemically measured using high-performance liquid chromatogr aphy. Nicotinic receptor agonists were applied once into the perfusion medi um for 2 min and nicotinic receptor antagonists were administered throughou t the experiments. The (-)-nicotine (3 x 10(-5) M)-induced noradrenaline re lease was abolished by tetrodotoxin and hexamethonium and partially blocked by dihydro-beta-erythroidine (up to 10(-5) M) (a relatively selective anta gonist of alpha 4 beta 2 nicotinic receptors) and abolished by mecamylamine (10(-5) M) (a relatively selective antagonist of alpha 3 beta 4 nicotinic receptors), but not influenced by alpha-bungarotoxin (3 X 10(-7) M) or alph a-conotoxin M (10(-6) M) (antagonists of alpha 7 nicotinic receptors). (+/- )-Epibatidine (3 X 10(-7) M) (a very potent, but non-selective agonist) and (-)-cytisine (3 X 10(-4) M) (an agonist of beta 4 nicotinic receptors) eff ectively evoked the release of noradrenaline, while (E)-N-methyl-4-(3-pyrid inyl)-3-butene-1-amine (RJR-2403) (up to 10(-4) M) (an agonist of alpha 4 b eta 2 nicotinic receptors) had no effect. The potency of these agonists was as followed; (+/-)-epibatidine >> (-)-nicotine > (-)-cytisine > > > RJR-24 03. These results are compatible with the published view that alpha 3 beta 4 nicotinic receptors an predominant in other parts of the autonomic nervou s system. These receptors (probably located on the gastric sympathetic gang lia) are involved in the release of noradrenaline from the rat stomach. (C) 2000 Elsevier Science B.V. All rights reserved.