Unrepeatable extracellular Ca2+-dependent contractile effects of cyclopiazonic acid in rat vascular smooth muscle.
Cyclopiazonic acid (CPA), a specific reversible inhibitor of Ca(2+)-pumps in sarcoplasmic reticulum, causes a slowly developing and subsequently diminishing characteristic contraction in endothelium-denuded rat vascular smooth muscle. We recently found that CPA-induced contractions were not completely repeatable in endothelium-denuded rat aorta and superior mesenteric artery. 10 microM CPA-induced contractions expressed as a percentage of 80 mM KCl-induced contraction were significantly decreased from 51.4+/-5.7% to 11.8+/-2.6% (P<0.0001) upon the second application in endothelium-denuded rat aorta, and this was not due to any irreversible cytotoxic effects of CPA. The decrease of CPA-induced contractile responses upon the second application was dependent on both types of blood vessels and doses of CPA upon the first application. CPA upon the second application in Ca(2+)-containing solutions did induce its characteristic contractions in the rings pretreated with Ca(2+)-free solutions or Ca(2+) entry blockers before and during its first application, suggesting that capacitative mode of Ca(2+) influx during the application of CPA might be responsible for the diminishment of contractions upon the second application. These data suggest that CPA by inducing a transient rise in cytosolic Ca(2+) level might cause a long-lasting upregulation of Ca(2+) extrusion across the plasma membrane in vascular smooth muscle cells and thus accelerate Ca(2+) efflux over a prolonged period, leading to unrepeatable contractile effects of CPA. Such long-lasting upregulation of Ca(2+) extrusion may contribute to the regulation of excitability of vascular smooth muscle cells and protect the cells against excitotoxic injury.
Zhang
Wen-Bo
WB
Research Institute of Basic Medical Sciences and Vascular Biology Research Group, College of Medicine, China Medical University, 91 Hue-Shih Road, Taichung, 40402, Taiwan.
Kwan
Chiu-Yin
CY
D000818:Animals; D001012:Aorta, Abdominal / Q000166:cytology; D001013:Aorta, Thoracic / Q000166:cytology; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000166:cytology; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D007211:Indoles; D002118:Calcium; C000543:cyclopiazonic acid