Role of K+ channels in M2 muscarinic receptor-mediated inhibition of noradrenaline release from the rat stomach.
Previously we reported the cholinergic M2 muscarinic receptor-mediated inhibition of noradrenaline release from the rat stomach (K. Yokotani, Y. Osumi. J Pharmacol Exp Ther. 1993;264:54-60). In the present study, we investigated the role of K+ channels in oxotremorine (a muscarinic receptor agonist)-induced inhibition of noradrenaline release using isolated, vascularly perfused rat stomach. The gastric postganglionic sympathetic nerves were electrically stimulated twice at 2.5 Hz for 1 min and test reagents were added during the second stimulation. The electrically evoked release of noradrenaline was augmented by tetraethylammonium and 4-aminopyridine (non-selective K+ channel blockers) and also by charybdotoxin (a blocker of big conductance Ca2+-activated K+ channel). On the other hand, apamin (a selective blocker of small conductance Ca2+-activated K+ channels) and glibenclamide (an ATP-activated K+ channel blocker) had no effect on the evoked noradrenaline release. Oxotremorine-induced inhibition of noradrenaline release was attenuated by tetraethylammonium and 4-aminopyridine, while the inhibition was not influenced by charybdotoxin, apamin, and glibenclamide. These results suggest that tetraethylammonium- and 4-aminopyridine-sensitive K+ channels (probably voltage-activated K+ channels) are involved in the muscarinic receptor-mediated inhibition of noradrenaline release from the rat stomach.
Nakamura
Kumiko
K
Department of Neuropharmacology, Program of Neural Integration, Graduate School of Medicine, Kochi University, Nankoku, Japan.
Okada
Shoshiro
S
Yamaguchi
Naoko
N
Shimizu
Takahiro
T
Yokotani
Keiko
K
Yokotani
Kunihiko
K
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D043585:Receptor, Muscarinic M2 / Q000502:physiology*; D013270:Stomach / Q000187:drug effects / Q000502:physiology*
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D043585:Receptor, Muscarinic M2; D009638:Norepinephrine