Adenosine receptors on human leukocytes. IV. Characterization of an A1/Ri receptor.
Adenosine (10(-9)-10(-6) mol/l) and R-phenylisopropyladenosine (10(-9)-10(-7) mol/l) partially inhibited the intracellular accumulation of cyclic AMP induced by isoproterenol, prostaglandin E1, histamine and 5'-N-ethylcarboxamidoadenosine in lymphocytes. In contrast, S-phenylisopropyladenosine, which is a poor agonist of the adenosine A1/Ri receptor, had essentially no inhibitory effect. 8-Phenyltheophylline, in low concentrations that do not inhibit cyclic AMP phosphodiesterase, completely blocked the inhibitory effect of R-phenylisopropyladenosine on the increase in cyclic AMP induced by prostaglandin E1. R-Phenylisopropyladenosine (10(-8)-10(-6) mol/l) also inhibited the cyclic AMP accumulation in lymphocytes induced by forskolin (10(-5) mol/l), which activates adenylate cyclase through direct interaction with the enzyme. We also investigated the presence of the adenosine A1/Ri receptor on human polymorphonuclear leukocytes. R-Phenylisopropyladenosine (3 x 10(-9)-10(-7) mol/l) abolished the stimulating effects of prostaglandin and forskolin on cyclic AMP accumulation in polymorphonuclear leukocytes. This effect was blocked by 8-phenyltheophylline and was not observed with the stereoisomer S-phenylisopropyladenosine. The results support the existence of an A1/Ri receptor that regulates cyclic AMP metabolism of human lymphocytes and polymorphonuclear leukocytes.
Marone
G
G
Department of Medicine, University of Naples Federico II, School of Medicine, Italy.
Petracca
R
R
Vigorita
S
S
Genovese
A
A
Casolaro
V
V
D000262:Adenylyl Cyclases / Q000187:drug effects; D005576:Colforsin / Q000037:antagonists & inhibitors; D000242:Cyclic AMP / Q000032:analysis; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D016131:Lymphocyte Subsets / Q000187:drug effects; D008214:Lymphocytes / Q000737:chemistry* / Q000187:drug effects / Q000201:enzymology; D009504:Neutrophils / Q000737:chemistry* / Q000201:enzymology; D010660:Phenylisopropyladenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000032:analysis*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D011983:Receptors, Purinergic; D005576:Colforsin; D010660:Phenylisopropyladenosine; D013806:Theophylline; D000242:Cyclic AMP; C028322:8-phenyltheophylline; D000262:Adenylyl Cyclases