title: Adenosine A(1) receptor stimulation inhibits alpha(1)-adrenergic activation of the cardiac sarcolemmal Na(+)/H(+) exchanger.
abstract: 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.
authors.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
authors.forename: M
authors.initials: M
authors.lastname: Avkiran
authors.forename: H
authors.initials: H
authors.lastname: Yokoyama
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D037342:Pertussis Toxin; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D012508:Sarcolemma / Q000201:enzymology*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D017923:Sodium-Hydrogen Exchangers; D010566:Virulence Factors, Bordetella; D014970:Xanthines; D010656:Phenylephrine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D037342:Pertussis Toxin; D013917:Thrombin; D000241:Adenosine; C082299:N-((1S,trans)-2-hydroxycyclopentyl)adenosine