Characterization of a stimulatory adenosine A(2a) receptor in adult rat ventricular myocyte

The expression and function of stimulatory adenosine A(2) receptor on the cardiac myocyte is not well defined. The objective of the present study is to characterize the A(2a) receptor in adult rat cardiac ventricular myocytes. After selection of an optimal lot of collagenase for myocyte isolation and for consistent measurement of adenosine-mediated responses, the A(1)-receptor pathway was inactivated by pertussis toxin and by the A(1)-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine. Effects of the adenosine agonist and antagonist on cardiac myocyte contractile amplitude and on adenosine 3',5'-cyclic monophosphate (cAMP) levels were determined. The A(2a)-receptor-selective agonist 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenosine (CGS-21680) caused a pronounced stimulation of myocyte contractile amplitude and an increase in the cAMP level, as did the nonselective agonists 5'-(N-ethylcarboxamido)adenosine (NECA) and adenosine. The A(2a)-receptor-selective antagonist 8-(3-chlorostyryl)caffeine blocked the NECA- and adenosine-induced positive inotropic response. Probing of myocyte RNA with a rat A(2a)-receptor cDNA demonstrated a 2.6-kb mRNA, corresponding to that encoding the A(2a) receptor. Together, data from contractile, cAMP, and RNA studies indicate that A(2a) receptors are expressed and are functionally coupled to stimulaton of cAMP accumulation and cardiac contractility in adult rat ventricular myocytes.