Effects of enprofylline on A1 and A2 adenosine receptors.
The effects of enprofylline were studied on A1 adenosine receptors of rat fat cells and on A2 adenosine receptors of human platelets and of guinea-pig lung. Enprofylline antagonized the 5'-N-ethylcarboxamidoadenosine (NECA)-induced stimulation of platelet adenylate cyclase activity with a KB of 130 microM. In human platelets, enprofylline did not antagonize but potentiated the NECA-induced inhibition of aggregation. This potentiation was abolished in the presence of the phosphodiesterase inhibitor papaverine. An adenosine antagonistic effect of enprofylline could not be evaluated on A2 receptors of guinea-pig lung because the xanthine enhanced basal and NECA-stimulated cyclic AMP accumulation. Enprofylline antagonized the N6-R-(-)-phenylisopropyladenosine (R-PIA)-induced inhibition of rat fat cell adenylate cyclase with a KB of 32 microM. The Ki value for inhibition of [3H]PIA binding to fat cell membranes was 45 microM. Enprofylline inhibited cyclic AMP phosphodiesterase activity of human platelets, guinea-pig lung and rat fat cells with Ki values of 15, 130 and 110 microM, respectively. The results show that enprofylline was nearly equipotent as antagonist at A1 and A2 adenosine receptors. Mechanisms other than adenosine antagonism or phosphodiesterase inhibition may be involved in the pharmacological effects of enprofylline.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011983:Receptors, Purinergic; D013268:Stimulation, Chemical; D013806:Theophylline / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology*
D001993:Bronchodilator Agents; D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D014970:Xanthines; D000244:Adenosine Diphosphate; D013806:Theophylline; C034347:enprofylline; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases