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  • Title: Effects of cyclopiazonic acid on phenylephrine-induced contractions in the rabbit ear artery.
    Author: Omote M, Mizusawa H.
    Journal: Br J Pharmacol; 1994 Jan; 111(1):233-7. PubMed ID: 7516801.
    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.
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