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

Tosun M, Erac Y, Selli C, Karakaya N. Sarcoplasmic-endoplasmic reticulum Ca -ATPase inhibition prevents endothelin A receptor antagonism in rat aorta. Am J Physiol Heart Circ Physiol 292: H1961–H1966, 2007. First published December 15, 2006; doi:10.1152/ajpheart.00298.2006.—This study tested whether sarcoplasmic-endoplasmic reticulum Ca -ATPase regulates the ability of endothelin receptor antagonist to inhibit the endothelin-1 constriction. The endothelin A receptor antagonist BQ-123 (1 M) completely relaxed constriction to 10 nM endothelin-1 in endothelium-denuded rat aorta. Challenge with cyclopiazonic acid (10 M), a sarcoplasmicendoplasmic reticulum Ca -ATPase inhibitor, during the plateau of endothelin-1 constriction enhanced the constriction by 30%. BQ123 relaxed the endothelin-1 plus cyclopiazonic acid constriction by only 10%. In contrast, prazosin (1 M), an -adrenergic receptor antagonist, still completely relaxed the 0.3 M phenylephrine constriction in the presence of cyclopiazonic acid. Verapamil relaxed the endothelin-1 plus cyclopiazonic acid constriction by 30%, whereas Ni and 2-aminoethoxydiphenyl borate, nonselective cation channel and store-operated channel blockers, respectively, completely relaxed the constriction. These results suggest that lowered sarcoplasmicendoplasmic reticulum Ca -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.