PMID: 9428616Jan 15, 1998Paper

Beta-adrenergic signal transduction in the failing and hypertrophied myocardium

Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
M BöhmP Schnabel

Abstract

A strong sympathetic activation has been observed in heart failure and is the cause of beta-adrenergic desensitization in this condition. On the receptor level there is downregulation of beta1-adrenergic receptors and uncoupling of beta2-adrenoceptors. The latter mechanism has been related to an increased activity and gene expression of beta-adrenoceptor kinase in failing myocardium, leading to phosphorylation and uncoupling of receptors. beta3-Adrenoceptors mediate negative inotropic effects, but alterations in these receptors are not known. In addition, an increase in inhibitory G protein alpha subunits (Gi alpha) has been suggested to be causally linked to adenylyl cyclase desensitization in heart failure. In contrast, the catalytic subunit of adenylyl cyclase, stimulatory G protein alpha and betagamma subunits, have been observed to be unchanged. Recent evidence shows that increases in Gi alpha also depress adenylyl cyclase in compensated cardiac hypertrophy both in monogenic and polygenic and in secondary hypertension. These increases of Gi alpha can suppress adenylyl cyclase in the absence of beta-adrenergic receptor downregulation. Since cardiac hypertrophy in pressure overload is a strong predictor of cardiac failure, t...Continue Reading

Citations

Sep 12, 2000·Current Hypertension Reports·M S Bray, E Boerwinkle
Mar 28, 2002·Pharmacology & Therapeutics·A A ArmoundasG F Tomaselli
May 20, 1999·Annual Review of Pharmacology and Toxicology·S R PostP A Insel
Mar 10, 2007·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Ming YuanToshio Ogihara
Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·M I MiyamotoR J Hajjar
May 29, 2004·Journal of Cardiovascular Pharmacology·Wendell S AkersSubbu Apparsundaram
Apr 4, 2000·Circulation Research·R J HajjarA Rosenzweig
Feb 4, 2011·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Yoshihiro IwamotoHiromi Rakugi
Feb 27, 2003·The Journal of Pharmacology and Experimental Therapeutics·Imène Tabbi-AnneniAlain Grynberg
Oct 12, 2000·Journal of Cardiovascular Pharmacology·P SchnabelM Böhm
Jan 25, 2000·American Journal of Physiology. Heart and Circulatory Physiology·H Yoshida, M Karmazyn
Feb 13, 2001·American Journal of Physiology. Heart and Circulatory Physiology·M JainR M Mortensen
Nov 9, 2000·Biochimica Et Biophysica Acta·S HammerschmidtS Neubauer
Jun 28, 2008·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Pippa M SchneeRoger J Bick

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