Regulatory effects of G protein-coupled receptors on cardiac sarcolemmal Na+/H+ exchanger activity: signalling and significance

TY - JOUR

T1 - Regulatory effects of G protein-coupled receptors on cardiac sarcolemmal Na+/H+ exchanger activity: signalling and significance

AU - Avkiran, M

AU - Haworth, R S

PY - 2003/4/1

Y1 - 2003/4/1

N2 - In cardiac myocytes, sarcolemmal Na+/H+ exchanger (NHE) activity is subject to regulation by a variety of G protein-coupled receptor (GPCR) systems. This regulation usually manifests as an increase in NHE activity (e.g. in response to the stimulation of alpha(1)-adrenergic, angiotensin AT(1), endothelin and thrombin receptors), although some GPCR systems have been shown to inhibit sarcolemmal NHE activity (e.g. beta(1)-adrenergic receptors) or to attenuate its stimulation by other ligands (e.g. adenosine A(1) and angiotensin AT(2) receptors). The pertinent molecular signalling mechanisms are only now beginning to be unravelled, with the extracellular signal regulated kinase/ribosomal S6 kinase pathway and the protein kinase C pathway both appearing to play critical roles in the stimulation of sarcolemmal NHE activity. GPCR-mediated regulation of sarcolemmal NHE activity is likely to play significant roles in modulating myocardial function in both physiological and pathophysiological conditions. These roles include the regulation of (1) myocardial pH(i) and contractility, (2) myocardial susceptibility to injury and dysfunction during ischaemia and reperfusion, and (3) myocardial hypertrophy in response to neurohormonal and mechanical stimuli. Greater understanding of the pertinent molecular signalling mechanisms distal to GPCR stimulation may reveal novel targets for therapeutic manipulation. (C) 2003 European Soceity of Cardiology. Published by Elsevier Science B.V. All rights reserved.

AB - In cardiac myocytes, sarcolemmal Na+/H+ exchanger (NHE) activity is subject to regulation by a variety of G protein-coupled receptor (GPCR) systems. This regulation usually manifests as an increase in NHE activity (e.g. in response to the stimulation of alpha(1)-adrenergic, angiotensin AT(1), endothelin and thrombin receptors), although some GPCR systems have been shown to inhibit sarcolemmal NHE activity (e.g. beta(1)-adrenergic receptors) or to attenuate its stimulation by other ligands (e.g. adenosine A(1) and angiotensin AT(2) receptors). The pertinent molecular signalling mechanisms are only now beginning to be unravelled, with the extracellular signal regulated kinase/ribosomal S6 kinase pathway and the protein kinase C pathway both appearing to play critical roles in the stimulation of sarcolemmal NHE activity. GPCR-mediated regulation of sarcolemmal NHE activity is likely to play significant roles in modulating myocardial function in both physiological and pathophysiological conditions. These roles include the regulation of (1) myocardial pH(i) and contractility, (2) myocardial susceptibility to injury and dysfunction during ischaemia and reperfusion, and (3) myocardial hypertrophy in response to neurohormonal and mechanical stimuli. Greater understanding of the pertinent molecular signalling mechanisms distal to GPCR stimulation may reveal novel targets for therapeutic manipulation. (C) 2003 European Soceity of Cardiology. Published by Elsevier Science B.V. All rights reserved.

U2 - 10.1016/S0008-6363(02)00782-4

DO - 10.1016/S0008-6363(02)00782-4

M3 - Literature review

SN - 1755-3245

VL - 57

SP - 942

EP - 952

JO - Cardiovascular Research

JF - Cardiovascular Research

IS - 4

ER -