PMID: 8596696Feb 1, 1996Paper

Endothelin-1 inhibits L-type Ca currents enhanced by isoproterenol in guinea-pig ventricular myocytes

Pflügers Archiv : European journal of physiology
L H XieS Sasayama

Abstract

To investigate the action of endothelin-1 (ET-1) on L-type Ca currents (ICa,L) in guinea-pig ventricular cells, whole-cell currents were recorded at approximately 36-37 degrees C in enzymatically isolated myocytes. ET-1 (> or =10 nM) suppressed the basal ICa,L to 79+/-8% of control at 20 nM. Bath application of isoproterenol (ISO; 10 nM) enhanced ICa,L to 192+/-28% with about a -10-mV shift of its relationship with membrane potential. ET-1 concentration dependently inhibited this ISO-enhanced ICa,L with a half-maximally inhibitory concentration (IC50) of 168 pM. The inhibitory actions of ET-1 were antagonised by BQ-123 (300 nM), cyclo(D-Asp-L-Pro-D-Val-L-Leu-D-Trp), a specific ETA receptor antagonist. Histamine-enhanced ICa,L was also suppressed by ET-1, but ICa, L potentiated by internal adenosine 3',5'-cyclic monophosphate (cAMP) was unaffected. Preincubation of myocytes with pertussis toxin (PTX, at 5 microgram/ml for >60 min at 36 degrees C) completely occluded the ET-1 action. Thus, stimulation of ETA receptors by subnanomolar ET-1 inhibits ICa,L via PTX-sensitive G-proteins.

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Citations

Oct 6, 1997·British Journal of Pharmacology·H TanakaM Yoshimura
Jul 21, 2007·British Journal of Pharmacology·K NishimaruM Endoh
May 13, 2011·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Ryan J ArantBarbara A Horwitz
Sep 7, 2000·Journal of Cardiovascular Pharmacology·T Watanabe, M Endoh
Mar 23, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Kimiaki KomukaiSatoshi Kurihara
Nov 15, 1997·The American Journal of Physiology·H YamaguchiH Nakaya

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