Noncoordinate regulation of cardiac Gs protein and beta-adrenergic receptors by a physiological stimulus, chronic dynamic exercise.

Downregulation of cardiac guanosine 5'-triphosphate-binding proteins in right atrium and left ventricle in pacing-induced congestive heart failure.

“…No prior studies have provided quantitative data expressed as activity per gram of tissue using both immunoblotting and ADP ribosylation in the heart. The activity of Gs per milligram protein that we find by quantitative immunoblotting is very similar to the amount that we previously reported by ELISA ( 12). Similar values obtained by two different techniques provide a high level of confidence in the quantitative capacity of our measurements.…”

“…If the porcine cardiac myocyte also has "spare" Gs, could a 20-27% decrease in Gs, as we report here, have biological meaning? We previously found that a 42% increase in RA Gs was associated with a 57% increase in the efficacy of isoproterenol to stimulate heart rate, suggesting that levels ofcardiac Gs may determine signal transduction efficiency ( 12). In heart failure, therefore, even though the amounts of adenylyl cyclase and ,BAR number may set limits upon maximal responsiveness, a decreased amount of Gs, albeit small, may further impair signal transduction efficiency.…”

Chronic nonocclusive coronary artery constriction in rats. Beta-adrenoceptor signal transduction and ventricular failure.

“…The left ventricle is faced with a high systemic vascular resistance and consequently operates as a pressure pump. On the other hand, the right ventricle is exposed to the low vascular resistance of the pulmonary circulation and acts as a volume pump (37). Moreover, the greater mechanical stimulus on the right ventricle during exercise (38) resulted in a down regulation of these receptors and in an increased amount of regulatory protein (37).…”

“…On the other hand, the right ventricle is exposed to the low vascular resistance of the pulmonary circulation and acts as a volume pump (37). Moreover, the greater mechanical stimulus on the right ventricle during exercise (38) resulted in a down regulation of these receptors and in an increased amount of regulatory protein (37). All these findings point to the possibility that the altered adrenergic responsiveness of the stressed myocardium can be modulated through postreceptor mechanisms.…”

Reduced beta-adrenergic receptor activation decreases G-protein expression and beta-adrenergic receptor kinase activity in porcine heart.

“…Previous studies from our laboratory and others have shown that sustained B-adrenergic receptor activation can influence the expression of not only cell surface /-adrenergic receptors, but also Gs and Gi in the heart (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Heart failure, a condition characterized in part by systemic neurohumoral adrenergic activation, is associated with reduced /3-adrenergic receptor expression at mRNA and protein levels (4, 5, [15][16][17] and, in some studies, with alterations in the expression of cardiac G-proteins (4,7,8,13,18).…”