Adenosine A receptor function in rat ventricular myocytes 12

Objective: This study was undertaken to investigate the functional significance of adenosine A receptor stimulation in a mammalian 2 ventricular myocyte preparation. Methods: Isolated contracting rat ventricular myocytes were employed to assess the contractile, adenylyl cyclase and cyclic AMP responses to adenosine receptor stimulation. Results: In single myocytes the presence of A receptors was 1 Ž . confirmed, as indicated by the A receptor agonist, phenylisopropyladenosine PIA , reducing by 60 and 74% the inotropic response and 1 activation of adenylyl cyclase, respectively, elicited by the b-adrenergic agonist, isoproterenol. An A receptor antagonist, dipropylcy1 Ž . clopentylxanthine DPCPX , prevented the antiadrenergic action of PIA. The A receptor agonist, carboxyethylphenethyl-aminoethyl2 Ž . carboxamido-adenosine CGS-21680; 0.01–10 mM increased myocyte inotropy in a concentration-dependent manner, reaching a Ž . Ž . maximum of 41–45%. Ethylcarboxamidoadenosine NECA , naphthyl-substituted aralkoxy-adenosine SHA-082 and adenosine in the presence of DPCPX also increased myocyte inotropy, as evidenced by increases in myocyte shortening, duration of shortening, time-to-peak shortening, time-to-75% relaxation and rate of maximal shortening. The agonists, however, did not effect the maximal rate Ž . Ž . of relaxation. The A receptor antagonists, chlorofuranyldihydrotri-azoloquinazolinimine CGS-15943 and chlorostyrylcaffeine CSC , 2 the latter selective for the A receptor, prevented the contractile responses elicited by the A agonists. Compared to the concentrations of 2a 2 A receptor agonists necessary to increase myocyte contractile variables, 3–12 times greater concentrations of the agonist were required 2 to increase myocyte adenylyl cyclase activity and cAMP levels. Conclusion: The results suggest the presence of adenosine A receptors 2a in the rat ventricular myocyte that appear to be responsible for an increase in inotropy via cAMP-dependent and -independent mechanisms. q 1997 Elsevier Science B.V.

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