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This Article Full Text Full Text (PDF) All Versions of this Article: 292/4/H1961    most recent 00298.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tosun, M. Articles by Karakaya, N. Search for Related Content PubMed PubMed Citation Articles by Tosun, M. Articles by Karakaya, N.

Sarcoplasmic-endoplasmic reticulum Ca²⁺-ATPase inhibition prevents endothelin A receptor antagonism in rat aorta

Department of Pharmacology, Faculty of Pharmacy, Ege University, Izmir, Turkey

Submitted 23 March 2006 ; accepted in final form 11 December 2006

This study tested whether sarcoplasmic-endoplasmic reticulum Ca²⁺-ATPase regulates the ability of endothelin receptor antagonist to inhibit the endothelin-1 constriction. The endothelin A receptor antagonist BQ-123 (1 µM) completely relaxed constriction to 10 nM endothelin-1 in endothelium-denuded rat aorta. Challenge with cyclopiazonic acid (10 µM), a sarcoplasmic-endoplasmic reticulum Ca²⁺-ATPase inhibitor, during the plateau of endothelin-1 constriction enhanced the constriction by 30%. BQ-123 relaxed the endothelin-1 plus cyclopiazonic acid constriction by only 10%. In contrast, prazosin (1 µM), an -adrenergic receptor antagonist, still completely relaxed the 0.3 µM phenylephrine constriction in the presence of cyclopiazonic acid. Verapamil relaxed the endothelin-1 plus cyclopiazonic acid constriction by 30%, whereas Ni²⁺ and 2-aminoethoxydiphenyl borate, nonselective cation channel and store-operated channel blockers, respectively, completely relaxed the constriction. These results suggest that lowered sarcoplasmic-endoplasmic reticulum Ca²⁺-ATPase activity selectively decreases the ability of endothelin receptor antagonist to inhibit the endothelin A receptor. The decreased antagonism may be related to the opening of store-operated channels and subsequent greater internalization of endothelin A receptor.

BQ-123; vascular smooth muscle; store-operated calcium; caveola