Use of A-192621 to provide evidence for involvement of endothelin ET(B)-receptors in endothelin-1-mediated cardiomyocyte hypertrophy

European Journal of Pharmacology
J P CullenB J McDermott

Abstract

Increased plasma levels of endothelin-1 correlate with the severity of left ventricular hypertrophy in vivo. The aim of the study was to determine the relative contribution of stimulation of endothelin ET(A) and endothelin ET(B) receptors, and the associated activation of protein kinase C, to the hypertrophic response initiated by endothelin-1 in adult rat ventricular cardiomyocytes maintained in culture (24 h). Endothelin-1 (10(-7) M) increased the total mass of protein and the incorporation of [14C] phenylalanine into protein to 26% and 25% greater (P<0.05) than respective basal values. The total content of RNA and the incorporation of 2-[14C] uridine into RNA were increased by 23% and 21%, respectively, by endothelin-1 (10(-8) M). Actinomycin D (5x10(-6) M), an inhibitor of transcription, abolished the incorporation of [14C] phenylalanine and the increased protein mass elicited by endothelin-1 (10(-8) M). The selective agonists at the endothelin ET(B) receptor, sarafotoxin 6c (10(-7) M) and endothelin-3 (10(-7) M), increased the incorporation of [14C] phenylalanine to 13% and 13% greater than respective basal values. The incorporation of [14C]phenylalanine in response to endothelin-1 (10(-7) M) was reduced by 50% (P<0.05) by...Continue Reading

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Citations

May 15, 2002·European Journal of Pharmacology·Suzanne M NichollBarbara J McDermott
Dec 29, 2009·Frontiers in Bioscience (Elite Edition)·Zhongjie Sun
Feb 7, 2006·Pharmacology & Therapeutics·Friedrich BrunnerAdelino F Leite-Moreira
Jul 25, 2006·Journal of Molecular and Cellular Cardiology·Raúl A DulceMaría C Camilión de Hurtado
Feb 28, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Graham R LeeBarbara J McDermott
Oct 17, 2008·Coronary Artery Disease·Aron Frederik PopovGerhard Anton Müller
Dec 31, 2005·Journal of Applied Physiology·Gin-Fu Chen, Zhongjie Sun

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