Nicotine-induced noradrenaline release from the isolated rat stomach by activation of L- and N-type calcium channels.
We examined the effect of nicotine on the release of endogenous noradrenaline (NA) from the isolated, vascularly perfused rat stomach. The stomach was perfused via the coeliac artery with Krebs-Ringer solution containing 10 microM pargyline at a constant flow rate of 4 ml per minute. Nicotine was once applied in the perfusion medium for 2 min. Nicotine (10(-6) - 10(-4) M) evoked NA release in a concentration-dependent manner. The nicotine (3 x 10(-5) M)-evoked NA release was abolished by hexamethonium and tetrodotoxin. Diltiazem and isradipine [blockers of L-type voltage-activated calcium channel (VACC)] and omega-conotoxin GVIA (a blocker of N-type VACC) also abolished this nicotine-evoked NA release. Previously we reported that N-type, but not L-type, VACCs are located on the gastric postganglionic sympathetic nerve terminals, since the NA release evoked by electrical stimulation of periarterial nerves around the left gastric artery (postganglionic sympathetic nerves) was abolished by omega-conotoxin GVIA, but not by diltiazem (Yokotani et al., Jpn. J. Pharmacol. 78, 75- 77, 1998). From these results, it was suggested that nicotine activates nicotinic acetylcholine receptors located on the sympathetic ganglia, thereby evoking NA release by activation of L-type VACC located on the gastric sympathetic ganglia and N-type VACC probably located on the sympathetic nerve terminals in the rat stomach.
Department of Pharmacology, Kochi Medical School, Nankoku, Japan.
M
M
Wang
S
S
Okada
Y
Y
Murakami
K
K
Yokotani
D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism; D018738:Hexamethonium / Q000494:pharmacology; D066298:In Vitro Techniques; D017275:Isradipine / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects* / Q000294:innervation; D013779:Tetrodotoxin / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D018738:Hexamethonium; D013779:Tetrodotoxin; D009538:Nicotine; D020866:omega-Conotoxin GVIA; D004110:Diltiazem; D009638:Norepinephrine; D017275:Isradipine