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

We characterized nicotinic acetylcholine receptor-mediated noradrenaline release from the isolated vascularly perfused rat stomach. The stomach was perfused via the coeliac artery with Krebs-Ringer solution at a constant flow rate of 4 ml per minute. Endogenous noradrenaline released into the perfusate was electrochemically measured using high-performance liquid chromatography. Nicotinic receptor agonists were applied once into the perfusion medium for 2 min and nicotinic receptor antagonists were administered throughout the experiments. The (-)-nicotine (3 x 10(-5) M)-induced noradrenaline release was abolished by tetrodotoxin and hexamethonium and partially blocked by dihydro-beta-erythroidine (up to 10(-5) M) (a relatively selective antagonist 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 alpha-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) effectively evoked the release of noradrenaline, while (E)-N-methyl-4-(3-pyridinyl)-3-butene-1-amine (RJR-2403) (up to 10(-4) M) (an agonist of alpha 4 beta 2 nicotinic receptors) had no effect. The potency of these agonists was as followed; (+/-)-epibatidine >> (-)-nicotine > (-)-cytisine > > > RJR-2403. These results are compatible with the published view that alpha 3 beta 4 nicotinic receptors an predominant in other parts of the autonomic nervous system. These receptors (probably located on the gastric sympathetic ganglia) are involved in the release of noradrenaline from the rat stomach. (C) 2000 Elsevier Science B.V. All rights reserved.