Nicotinic receptors involved in gastric noradrenaline release evoked by electrical stimulation of the splanchnic nerve in rats

In the present experiment, we tried to compare the functional nicotinic rec eptors activated by electrical stimulation of the greater splanchnic nerve (containing preganglionic sympathetic nerves) to those activated by (-)-nic otine, using the isolated rat stomach. The stomach was perfused with Krebs- Ringer solution and endogenous noradrenaline released into the perfusate wa s electrochemically measured using high-performance liquid chromatography. The release of noradrenaline evoked by repeated application of 30 mM (-)-ni cotine rapidly declined. However, the release of noradrenaline evoked by el ectrical stimulation of the splanchnic nerve at 2.5 Hz was not disturbed by the appearance of tachyphylaxis for (-)-nicotine. The (-)-nicotine-induced release of noradrenaline was abolished by diltiazem, but this reagent had no effect on the electrically evoked release of noradrenaline. The electric ally evoked release of noradrenaline was not influenced by atropine, but wa s reduced to approximately 50% by hexamethonium. This electrically evoked r elease of noradrenaline was not influenced by a-bungarotoxin, a-conotoxin I mI (blockers of alpha7 nicotinic receptors) or dihydro-P-erythroidine (a bl ocker of alpha4 beta2 nicotinic receptors), but was reduced to about 50% by mecamylamine (a blocker of alpha3 beta4 nicotinic receptors). The (-)-nico tine-induced release of noradrenaline has already been shown to be partiall y blocked by dihydro-P-erythroidine and to be abolished by mecamylamine as shown by Yokotani et al. [Eur. J. Pharmacol. 402 (2000) 223.]. These result s suggest that the gastric release of noradrenaline in response to electric al stimulation of the greater splanchnic nerve is mediated by cholinergic ( probably ganglionic (alpha3 beta4 nicotinic receptor-mediated) and non-chol inergic mechanisms in rats. However, the functional nicotinic receptor acti vated by electrical stimulation of the splanchnic nerve seems to be differe nt in character from that activated by (-)-nicotine. (C) 2001 Published by Elsevier Science B.V.