Functional and biochemical evidence of a specific adenosine A2/Ra receptor on human platelets.
5'-N-ethylcarboxamideadenosine (NECA) greater than 2-chloroadenosine greater than adenosine greater than (-)-N6-(R-phenyl-isopropyl)-adenosine [(-)-R-PIA] greater than (+)-N6-(S-phenyl-isopropyl)-adenosine [(+)-S-PIA] inhibited in vitro human platelet aggregation in a dose-dependent fashion. 6-nitrobenzylthioinosine and dipyridamole, which inhibit adenosine uptake, and erythro-9-(2-hydroxy-3-nonyl)-adenine, which blocks adenosine metabolism, did not impair the inhibition induced by NECA and adenosine. 8-phenyltheophylline and theophylline, two competitive antagonists of adenosine receptors, blocked the inhibition of platelet aggregation caused by NECA and adenosine. NECA greater than 2-chloroadenosine greater than adenosine greater than (-)-R-PIA greater than (+)-S-PIA increased platelet cyclic adenosine monophosphate (cAMP) levels in a dose-dependent fashion. A significant linear correlation (r = 0.70, p less than 0.001) was found between the increase of platelet cAMP and the inhibition of platelet aggregation induced by adenosine and its analogs. 8-phenyltheophylline, which is a competitive antagonist of adenosine in platelets, also blocked the cAMP accumulation caused by NECA. These data suggest that NECA and other adenosine analogs activate a specific cell surface adenylate cyclase-linked adenosine receptor whose properties are similar to those of an adenosine A2/Ra receptor.
Quattrin
S
S
I Clinica Medica, II Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli, Italy.
Genovese
A
A
Cirillo
R
R
Formisano
S
S
Marone
G
G
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000244:Adenosine Diphosphate; D000328:Adult; D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology; D000001:Calcimycin; D003094:Collagen; D000242:Cyclic AMP / Q000378:metabolism; D004837:Epinephrine; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000032:analysis / Q000187:drug effects / Q000502:physiology*; D014970:Xanthines / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D011983:Receptors, Purinergic; D014970:Xanthines; C008514:methylxanthine; D000001:Calcimycin; D000244:Adenosine Diphosphate; D003094:Collagen; D000242:Cyclic AMP; D000241:Adenosine; D004837:Epinephrine