title: Effects of cyclopiazonic acid on phenylephrine-induced contractions in the rabbit ear artery.
abstract: 1. Upon stimulation with phenylephrine, the rabbit ear artery displays endothelium-regulated rhythmic contractions, which may be attributed to the periodical activation of the dihydropyridine-sensitive Ca2+ channel, presumably regulated by the Ca(2+)-activated K+ channel. The effect of cyclopiazonic acid (CPA), an inhibitor of the Ca(2+)-ATPase of the sarcoplasmic reticulum (SR), on phenylephrine-induced contractions was examined in endothelium-denuded rabbit ear arteries suspended in an organ chamber for isometric tension recordings. 2. Phenylephrine-induced tonic contractions were converted to rhythmic ones by the addition of CPA. 3. The CPA-induced rhythmic contractions were abolished by the blockade of the dihydropyridine-sensitive Ca2+ channel and the Ca(2+)-activated K+ channel by nifedipine and charybdotoxin, respectively. In contrast, glibenclamide, an ATP-sensitive K+ channel antagonist, had no effect on the CPA-induced rhythmic responses. 4. CPA attenuated both Ca2+ repletion by the SR and Ca2+ influx across the plasmalemma without having a significant effect on Ca2+ release from the SR, as evaluated by phenylephrine-induced contractions. In contrast, these three parameters were not altered by the presence of the endothelium. 5. These findings indicate that the CPA-induced rhythmic contractions in the endothelium-denuded rabbit ear artery may be induced by the same ionic mechanism as endothelium-regulated rhythmic responses, by which the K+ channel could regulate the probability of the Ca2+ channel being opened. The CPA-induced rhythmic contractions may correlate with the inhibitory effects of CPA on the SR function, although this is not true for the endothelium-regulated rhythmic contractions.
authors.affiliation: Development Laboratories Hirakata Center, Marion Merrell Dow, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Omote
authors.forename: H
authors.initials: H
authors.lastname: Mizusawa
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D018999:Charybdotoxin; D004095:Dihydropyridines / Q000494:pharmacology; D004423:Ear / Q000098:blood supply; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012604:Scorpion Venoms / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007211:Indoles; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms; D018999:Charybdotoxin; D010656:Phenylephrine; C038806:1,4-dihydropyridine; D000252:Calcium-Transporting ATPases; D009543:Nifedipine; D002118:Calcium; C000543:cyclopiazonic acid