These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Cyclopiazonic acid, an inhibitor of Ca(2+)-ATPase in sarcoplasmic reticulum, increases excitability in ileal smooth muscle.
    Author: Uyama Y, Imaizumi Y, Watanabe M.
    Journal: Br J Pharmacol; 1993 Oct; 110(2):565-72. PubMed ID: 8242231.
    Abstract:
    1. Effects of cyclopiazonic acid (CPA), a specific inhibitor of Ca(2+)-ATPase in endo- and sarcoplasmic reticulum (ER/SR), on contractile responses, cytosolic Ca2+ concentration and spontaneous electrical activity were examined in ileal longitudinal smooth muscle strips. 2. After intracellular stored Ca2+ in intact ileal strips was depleted by application of 25 mM caffeine in Ca(2+)-free solution, Ca(2+)-loading was performed in the absence or presence of 10 microns CPA in a standard solution containing 2.2 mM Ca2+. Subsequent application of caffeine in Ca(2+)-free solution induced a phasic contraction which was significantly smaller in the strip pretreated with CPA than that in the control. 3. Spontaneous and 20 mM K(+)-induced contractions in the presence of 1 microM atropine were markedly enhanced by 1-30 microM CPA, whereas that induced by 80 mM K+ was not. The magnitude of repetitive transient elevation of cytosolic Ca2+ concentration ([Ca2+])i) and concomitant phasic contractions were markedly enhanced by CPA. The effects were abolished by 10 microM verapamil and restored by 10 microM Bay K 8644. 4. Application of 10 microM CPA depolarized the cell by about 5 mV, decreased the action potential (AP) afterhyperpolarization and markedly increased the frequency of spontaneous AP. These effects were mimicked by 100 nM charybdotoxin. 5. The rate of decay of [Ca2+]i and tension after the bathing solution was changed from one containing 140 mM K+ and 2.2 mM Ca2+ to one containing 5.9 mM K+ and 0 mM Ca2+ was significantly slowed when 10 microM CPA was added to the latter solution. 6. These results indicate that CPA enhances ileal smooth muscle excitability and increases Ca2+-influx through voltage-dependent Ca2+ channels. The effect may be consistent with the hypothesis that CPA-induced decrease in stored Ca due to Ca-pump inhibition reduces the Ca2+-dependent K+ current and indirectly enhances Ca2+-influx through membrane activity resulting from the increased excitability.Direct evidence for the regulation of Ca2+ channel activity by intracellular Ca storage sites was not obtained in the present study.
    [Abstract] [Full Text] [Related] [New Search]