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

1. In spontaneously beating atria isolated from reserpine-treated guinea-pig adenosine, AMP, ADP, ATP (2 microM) and alpha, beta-methylene ATP (0.4 microM) 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 microM) was completely inactive. 2. The early, negative influences were antagonized by 8-phenyltheophylline (0.5-10 microM), an alkylxanthine that competes with purines for P1 receptors. 3. The late, positive response was potentiated by 8-phenyltheophylline (0.5-10 microM) and suppressed by quinidine (5 microM), 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 microM) 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 stimulatory effects of adenine compounds.