Stimulatory Subtpe of Adenosine Receptor in Fetal Chick Ventricular Myocytes

Ventricular and atrial myocytes cultured from chick embryos 14 days in ovo were used as model systems to study cardiac adenosine receptors. In membranes of ventricular cultures, blocking of the A1-adenosine receptor pathway by the A1-selective antagonist 8-cyclopentyl-1,3 -dipropylxanthine (DPCPX) or by pertussis toxin treatment of the myocyte resulted in a significant adenosine agonist-mediated stimulation of the adenylate cyclase activity. The maximal increases in adenylate cyclase activity caused by the equipotent or the A2-adenosine receptorselective agonists (from 52.1±3% to 63±10% [mean±SEM]) were significantly greater than those caused by the A1-selective agonists (from 11+5% to 34.6+7%) (p<0.01, by t test, n=4-8). However, in membranes of atrial myocytes, when Al-subtype had been blocked, the various adenosine agonists had no effect on the adenylate cyclase activity. Whether the stiLmulatory adenylate cyclase-coupled adenosine receptor is also capable of stimulating contractility in the intact ventricular myocyte was next investigated. In ventricular but not in atrial cells, the various adenosine agonists caused an increase in the contractile amplitude in the presence of DPCPX or in myocytes preexposed to pertussis toxin. The increase in contraction amplitude caused by each agonist was expressed as percent of maximum (maximum is the increase in contractility, caused by 2.4 mM calcium). In the pertussis toxin-treated myocyte, the maximal increases caused by the equipotent or A2-agonists (NECA, MECA, CV-1808, and CGS21680, from 49.6+±3% to 52.5+6%, n=8-12) were significantly greater than those elicited by the Al-agonists (2-CADO, S-PIA, R-PIA, and DCCA, from 12±4% to 37+3%, n=8) (p<0.05, by t test). These data demonstrated that a stimulatory adenosine receptor, likely the A2-adenosine receptor, was present on the ventricular but not the atrial myocytes and was linked directly to