Effects of K(ATP) channel modulators on acetylcholine release from guinea-pig isolated atria and small intestine.
The effects of K(ATP) channel blockers (glibenclamide, HMR 1883, HMR 1372) and openers (cromakalim, pinacidil, diazoxide) on the electrically-evoked (5 Hz) release of [(3)H]acetylcholine were studied in isolated guinea-pig atria and myenteric plexus-longitudinal muscle preparations which had been preincubated with [(3)H]choline. Atria: Cromakalim (0.3 microM and 1 microM), pinacidil (10 microM) and diazoxide (30 microM) significantly reduced the stimulation-evoked release of [(3)H]acetylcholine. The inhibition produced by cromakalim and pinacidil was prevented by 1 microM of either HMR 1883, HMR 1372 or glibenclamide. The blockers alone significantly increased the release at concentrations of 30 microM, whereas 1 microM and 10 microM had no effect. Myenteric plexus-longitudinal muscle preparation: The electrically-evoked release of [(3)H]acetylcholine was not affected by K(ATP) channel blockers or openers. In contrast, the contractions of the longitudinal muscle caused by electrical stimulation or by carbachol were strongly inhibited by 1 microM cromakalim which suggests that the relaxant effect of the K(ATP) channel openers is exclusively a direct effect on intestinal smooth muscle. The findings suggest that blockade of activated K(ATP) channels in vagal nerves of guinea-pig atria stimulates acetylcholine release, and that this effect may contribute to the antiarrhythmic actions of K(ATP) channel blockers. By contrast, release of acetylcholine from guinea-pig myenteric plexus is not modulated by K(ATP) channels which suggests heterogeneity of K(ATP) channel distribution in peripheral autonomic nerves.
Kilbinger
H
H
Pharmakologisches Institut, Universität Mainz, 55101 Mainz, Germany. KILBINGE@mail.uni-mainz.de
Krause
A
A
Mang
C F
CF
Englert
H
H
Wirth
K
K
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D016275:Atrial Function; D019806:Cromakalim / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D020110:Pinacidil / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013449:Sulfonamides; D019806:Cromakalim; D020110:Pinacidil; C114623:clamikalant; D013890:Thiourea; D000109:Acetylcholine; D003981:Diazoxide; D005905:Glyburide