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pubmed:abstractText |
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]adenosine (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 microM) had no effect on NHE activity. However, co-administration of GR79236 inhibited, in a concentration-dependent manner, the stimulation of NHE activity by the alpha(1)-adrenoceptor agonist phenylephrine (10 microM). The inhibitory effect of GR79236 (10 microM) was abolished by (1) the selective A(1) antagonist 1,3-dipropyl-8-cyclopentylxanthine (0.1 microM), confirming an A(1) receptor-mediated action, and (2) pre-treatment with pertussis toxin (5 microgram 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.
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pubmed:affiliation |
Centre for Cardiovascular Biology and Medicine, King's College London, The Rayne Institute, St Thomas' Hospital, London SE1 7EH. metin.avkiran@kcl.ac.uk
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