Negative and positive influences exerted by purine compounds on isolated guinea-pig atria

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Abstract
1 In spontaneously beating atria isolated from reserpine-treated guinea-pig adenosine, AMP, ADP, ATP (2 .mu.M) and .alpha.,.beta.-methylene ATP (0.4 .mu.M) induced a dual effect: a short lasting negative response, characterized by a reduction in contractile force and in frequency rate, followed by a positive phase of increased inotropism and chronotropism. N6-phenylisopropyladenosine (5 nM) induced only the depressant effects whereas inosine (2 .mu.M) was completely inactive. 2 The early, negative influences were antagonized by 8-phenyltheophylline (0.5-10 .mu.M), an alkylxanthine that competes with purines for P1 receptors. 3 The late, positive response was potentiated by 8-phenyltheophylline (0.5-10 .mu.M) and suppressed by quinidine (5 .mu.M), that blocks the effects of adenine compounds mediated by P2 receptors. 4 In spontaneously beating as well as in electrically driven atria, desensitization of P2 purinoceptors by long lasting exposure to .alpha.,.beta.-methylene ATP (8 .mu.M) abolished the late positive response to ATP. In preparations treated with both .alpha.,.beta.-methylene ATP and 8-phenyltheophylline, ATP was ineffective. 5 These results suggest that, besides P1 receptors, P2 receptors are also present in guinea-pig atria, mediating stimulating effects of adenine compounds.