Inhibition by purines of the inotropic action of isoprenaline in rat atria

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Abstract
1 The effects of a series of adenosine derivatives were examined on the catecholamine-stimulated electrically-driven rat left atrium in vitro. 2 All the purines tested reduced the positive inotropic action of isoprenaline, 0.1 μM, with the potency order: L-N6-phenlylisopropyladenosine (L-PIA) > 5′-N-ethylcarboxamide adenosine (NECA) > D-PIA > 2-chloroadenosine > adenosine. Dipyridamole did not change the IC50 of adenosine. The adenosine deaminase inhibitor, 2′deoxycoformycin, produced a small but nonsignificant shift to the left of the adenosine concentration-response curve. 3 The cardiac depressant effects of these purines were reversed by theophylline and the IC50 values were unchanged in the presence of atropine or in atria taken from reserpine-treated rats. 4 It is concluded that the purine receptor mediating these effects should not be classified on the A1/A2 system. The relationship between functionally characterized purine receptors and those originally defined as modulating adenylate cyclase is discussed.