Adenosine A1 receptor stimulation inhibits α1-adrenergic activation of the cardiac sarcolemmal Na+/H+ exchanger

Sarcolemmal Na+/H+ exchanger (NHE) activity is increased by stimulation of G(q) protein-coupled receptors (G(q)PCRs), but the roles of other GPCRs are largely unknown. We determined the effects of N-[(1S,trans)-2-hydroxycyclopentyl]adeno (GR79236), a selective agonist of the G(i)PCR adenosine A(1) receptor, on sarcolemmal NHE activity in adult rat ventricular myocytes (n = 8 - 10 per group). NHE activity was indexed by the H+ efflux rate after intracellular acidification, measured by microepifluorescence. GR79236 alone (0.01 - 10 muM) had no effect on NHE activity. However, coadministration of GR79236 inhibited, in a concentration-dependent manner, the stimulation of NHE activity by the alpha (1)-adrenoceptor agonist phenylephrine (10 muM). The inhibitory effect of GR79236 (10 muM) was abolished by (1) the selective Al antagonist 1,3-dipropyl-8-cyclopentylxanthine (0.1 muM), confirming an A(1) receptor-mediated action, and (2) pre-treatment with pertussis toxin (5 mug ml(-1) for 60 min), indicating a G(i) protein-mediated mechanism. Our data suggest the existence of inhibitory crosstalk between the G(i)PCR adenosine A(1) receptor and the G(q)PCR alpha (1)-adrenoceptor in the regulation of sarcolemmal NHE activity.