Summary
The effects of several 5′-carboxamide derivatives of adenosine on stimulatory (R a) adenosine receptors of human platelets and inhibitory (R i) adenosine receptors of rat fat cells have been compared. 5′-N-Cyclopropylcarboxamidoadenosine (CPCA) and 5′-N-ethylcarboxamidoadenosine (NECA) most potently inhibited ADP-induced aggregation of human platelets as shown by IC50-values of 0.24 and 0.34 μmol/l. 5′-N-Methylcarboxamidoadenosine (MECA; IC50 0.81 μmol/l) and 5′-N-carboxamidoadenosine (NCA; IC50 2.1 μmol/l) were less potent, whereas adenosine, 2-chloroadenosine and (-)N6-phenylisopropyladenosine [(-)PIA] exhibit IC50-values of about 1.5 μmol/l. Nearly the same rank order of potency was obtained for stimulation of adenylate cyclase activity of platelet membranes and for inhibition of [3H]NECA binding to human platelets. In order to examine the effects of the carboxamide analogues on R i adenosine receptors of rat fat cells inhibition of lipolysis and adenylate cyclase were studied. (-)PIA was the most potent inhibitor of lipolysis as shown by an IC50 of 0.5 nmol/l, followed by CPCA (IC50 1.1 nmol/l) and NECA (IC50 1.3 nmol/l), whereas MECA (IC50 17.9 nmol/l) and NCA (IC50 20.1 nmol/l) were much less potent than NECA in inhibiting lipolysis. Similar results were obtained for inhibition of adenylate cyclase activity of fat cell membranes and for competition with [3H]PIA binding to fat cell membranes. The relative potencies of the adenosine analogues at both receptor subclasses were calculated from the ratio of the IC50-values for inhibition of platelet aggregation and of lipolysis. (-)PIA showed the highest selectivity for R i receptors as indicated by a 2,900-fold lower IC50 for the antilipolytic than for the antiaggregatory effect. The R a/R i activity ratio for NECA was about 260, for CPCA 220, for NCA 105 and for MECA 45. These results indicate that all 5′-carboxamide adenosine derivatives are more potent agonists at R i receptors than at R a receptors. Since MECA has a higher selectivity for R a receptors than NECA, it may be useful for the characterization of stimulatory adenosine receptors in different tissues.
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Ukena, D., Böhme, E. & Schwabe, U. Effects of several 5′-carboxamide derivatives of adenosine on adenosine receptors of human platelets and rat fat cells. Naunyn-Schmiedeberg's Arch. Pharmacol. 327, 36–42 (1984). https://doi.org/10.1007/BF00504989
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DOI: https://doi.org/10.1007/BF00504989