PMID: 8723031Feb 1, 1996

Selective inhibition of oxalate-stimulated Ca2+ transport by cyclopiazonic acid and thapsigargin in smooth muscle microsomes

Canadian Journal of Physiology and Pharmacology
P J DarbyE E Daniel

Abstract

45Ca2+ uptake and efflux studies were performed on membranes prepared from dog mesenteric artery and rat vas deferens. Oxalate-stimulated, ATP-dependent Ca2+ uptake in microsomal vesicles, a property characteristic of sarcoplasmic reticulum, was completely inhibited in a concentration-dependent manner by cyclopiazonic acid (0.1-30 microM) and thapsigargin (10 nM-10 microM). Using discontinuous sucrose gradient centrifugation, rat vas deferens microsomes were separated into two fractions, one enriched in plasma membrane (F2), the other enriched in sarcoplasmic reticulum (F3). The F3 fraction had a major increase in Ca2+ uptake in the presence of oxalate, which was completely inhibited by either cyclopiazonic acid or thapsigargin. In the F2 fraction Ca2+ uptake in the presence of oxalate was lower than in F3 and was not completely inhibited by thapsigargin and cyclopiazonic acid. Instead, the F2 fraction had a thapsigargin-insensitive and cyclopiazonic acid insensitive, saponin-sensitive component of uptake, which probably represents Ca2+ uptake by plasma membrane. In the absence of oxalate, the inhibition of Ca2+ uptake by saponin and cyclopiazonic acid or thapsigargin was additive in the F2 and F3 fractions, suggesting that cyc...Continue Reading

References

Nov 1, 1992·The Journal of Membrane Biology·J WangR S Eisenberg
Apr 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·O ThastrupA P Dawson
Dec 1, 1985·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·W P NorredJ W Dorner
Mar 1, 1995·Trends in Pharmacological Sciences·C van BreemenI Laher

Related Concepts

Cyclopiazonic acid
2-aminoisobutyric acid,14C-labeled
Ca(2+)-Transporting ATPase
Aminoisobutyric Acids
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Canis familiaris
Dose-Response Relationship, Drug
Drug Interactions
Enzyme Inhibitors
Indoles

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