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 receptors activated by electrical stimulation of the greater splanchnic nerve (containing preganglionic sympathetic nerves) to those activated by (-)-nicotine, using the isolated rat stomach. The stomach was perfused with Krebs-Ringer solution and endogenous noradrenaline released into the perfusate was electrochemically measured using high-performance liquid chromatography. The release of noradrenaline evoked by repeated application of 30 mM (-)-nicotine rapidly declined. However, the release of noradrenaline evoked by electrical 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 electrically evoked release of noradrenaline was not influenced by atropine, but was reduced to approximately 50% by hexamethonium. This electrically evoked release of noradrenaline was not influenced by alpha-bungarotoxin, alpha-conotoxin ImI (blockers of alpha 7 nicotinic receptors) or dihydro-beta-erythroidine (a blocker of alpha 4 beta 2 nicotinic receptors), but was reduced to about 50% by mecamylamine (a blocker of alpha 3 beta 4 nicotinic receptors). The (-)-nicotine-induced release of noradrenaline has already been shown to be partially blocked by dihydro-beta-erythroidine and to be abolished by mecamylamine as shown by Yokotani et al. [Eur. J. Pharmacol. 402 (2000) 223.]. These results suggest that the gastric release of noradrenaline in response to electrical stimulation of the greater splanchnic nerve is mediated by cholinergic (probably ganglionic alpha 3 beta 4 nicotinic receptor-mediated) and non-cholinergic mechanisms in rats. However, the functional nicotinic receptor activated by electrical stimulation of the splanchnic nerve seems to be different in character from that activated by (-)-nicotine.
Yokotani
K
K
Department of Pharmacology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan. yokotani@dtn.am400gw.kochi-ms.ac.jp
Okada
S
S
Murakami
Y
Y
Nakamura
K
K
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020916:Conotoxins / Q000494:pharmacology; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004558:Electric Stimulation; D005753:Gastric Mucosa / Q000378:metabolism*; D018738:Hexamethonium / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000502:physiology*; D013153:Splanchnic Nerves / Q000502:physiology*; D013270:Stomach / Q000187:drug effects / Q000294:innervation
D002038:Bungarotoxins; D002121:Calcium Channel Blockers; D020916:Conotoxins; D011978:Receptors, Nicotinic; C087686:alpha-conotoxin ImI; D004079:Dihydro-beta-Erythroidine; D018738:Hexamethonium; D008464:Mecamylamine; D009538:Nicotine; D001285:Atropine; D004110:Diltiazem; D009638:Norepinephrine