PMID: 8606620Jan 1, 1996Paper

Inhibition of cyclic AMP accumulation by endothelin is pertussis toxin sensitive and calcium independent in isolated adult feline cardiac myocytes

Life Sciences
L G Jones

Abstract

The aims of this study were to determine whether endothelin-1 (ET-1), a positive inotropic agent, altered the production of cyclic AMP (cAMP) in adult feline cardiac myocytes and to characterize the effect with respect to G-protein-coupling and calcium regulation of adenylyl cyclase. ET-1 inhibited basal and/or stimulated cAMP accumulation in the intact cardiac myocyte and in membrane preparations in a dose-dependent manner. In intact cells, maximal inhibition of forskolin-stimulated cAMP accumulation was 90-95% with an EC50 of 5 x 10(-10) M. Inhibition of isoproterenol-stimulated cAMP was biphasic with maximal inhibition of 70% observed by 10(-11)M; at higher doses inhibition was not consistently observed. The inhibitory response to ET-1 occurred in the absence or presence of isobutylmethylxanthine suggesting that activation of cAMP phosphodiesterases was not the means for reducing cAMP levels. Prior exposure of cardiac myocytes to 100ng/ml pertussis toxin blocked the inhibitory action of ET-1, indicating that this response is mediated through the involvement of a pertussis toxin-sensitive G-protein such as Gi. Studies carried out in the absence of extracellular calcium and under conditions of cell-loading with the intracellul...Continue Reading

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Citations

Jul 25, 2003·Journal of Molecular and Cellular Cardiology·Peter H Sugden
Dec 13, 2005·The FEBS Journal·Angelika HorstmeyerThomas Krieg
Jun 19, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Masaki OkajimaMichel Lavallée
Sep 5, 2009·Journal of Cardiovascular Pharmacology·Angel Luis García-VillalónGodofredo Diéguez
Mar 6, 2010·American Journal of Respiratory Cell and Molecular Biology·Florian BossardChantal Gauthier
Sep 7, 2000·Journal of Cardiovascular Pharmacology·T Watanabe, M Endoh

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