Bosentan, a novel synthetic mixed-type endothelin receptor antagonist, attenuates acute gastric mucosal lesions induced by indomethacin and HCl in the rat: Role of endogenous endothelin-1

1997 ◽  
Vol 32 (2) ◽  
pp. 164-170 ◽  
Author(s):  
Kazuhiko Matsumaru ◽  
Hiromasa Kashimura ◽  
Mahmudul Hassan ◽  
Akira Nakahara ◽  
Takashi Hayashi ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Mixed Type ◽  
Endothelin Receptor Antagonist ◽  
Endothelin Receptor ◽  
Gastric Mucosal Lesions ◽  
Endothelin 1 ◽  
Mucosal Lesions

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

2007 ◽  
Vol 292 (4) ◽  
pp. H1961-H1966 ◽  
Author(s):  
M. Tosun ◽  
Y. Erac ◽  
C. Selli ◽  
N. Karakaya
Keyword(s):  
Endoplasmic Reticulum ◽  
Receptor Antagonist ◽  
Cyclopiazonic Acid ◽  
Rat Aorta ◽  
Endothelin Receptor Antagonist ◽  
Endothelin Receptor ◽  
Atpase Inhibitor ◽  
Endothelin 1 ◽  
Endothelin A Receptor ◽  
Endothelin A

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 α-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.

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