The effects of chronic caffeine administration on peripheral adenosine receptors.
Rat platelets and adipocytes were used as models to investigate alterations of the A2- and of the A1-adenosine receptor-adenylate cyclase system of peripheral cells caused by chronic caffeine administration. The maximum effects of 5'-N-ethylcarboxamidoadenosine (NECA) to stimulate adenylate cyclase activity in suspensions of platelet membranes and to inhibit aggregation were significantly greater with platelets from caffeine-treated rats than from control rats. The effects of 1 to 100 nM prostaglandin E1 to inhibit platelet aggregation and to stimulate adenylate cyclase activity in platelet membranes were also significantly greater with caffeine-treated than with control rats. These data suggest that the increased ability of NECA to inhibit platelet aggregation after chronic caffeine ingestion was a result of increased cyclic AMP accumulation induced by this agonist. The increased stimulatory effect of NECA on adenylate cyclase in platelet membranes could be due to an increased A2-adenosine receptor number and/or an increased functional coupling between A2-adenosine receptor and stimulatory guanine nucleotide binding proteins. In contrast, although A1-receptor number was 37% higher in fat cell membranes from caffeine-treated rats than in those from control rats, increased A1-adenosine receptor-mediated inhibition of lipolysis and of adenylate cyclase was not detected. Thus, chronic caffeine consumption causes alterations in the response of some but not all peripheral cell types to agonists of adenosine receptors.
Zhang
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Y
Department of Pharmacology, Vanderbilt University, School of Medicine, Nashville, Tennessee.
Wells
J N
JN
D000262:Adenylyl Cyclases / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002110:Caffeine / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D005576:Colforsin / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects*; D014970:Xanthines / Q000378:metabolism
D011983:Receptors, Purinergic; D014970:Xanthines; D005576:Colforsin; D002110:Caffeine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000262:Adenylyl Cyclases