Copyright © 1990 by The American Society for Pharmacology and Experimental Therapeutics Printed in U.S.A. Effects of Chronic Caffeine Administration on Peripheral

Rat platelets and adipocytes were used as models to investigate of increased cyclic AMP accumulation induced by this agonist. alterations of the alpha-2 and of the alpha-i adenosine receptor- The increased stimulatory effect of NECA on adenylate cyclase adenylate cyclase system of peripheral cells caused by chronic in platelet membranes could be due to an increased alpha-2 caffeine administration. The maximum effects of 5’-N-ethylcar- adenosine receptor number and/or an increased functional cou-boxamidoadenosine (NECA) to stimulate adenylate cyclase ac- pling between alpha-2 adenosine receptor and stimulatory gua-tivity in suspensions of platelet membranes and to inhibit aggre- nine nucleotide binding proteins. In contrast, although alpha-i gation were significantly greater with platelets from caffeine- receptor number was 37 % higher in fat cell membranes from treated rats than from control rats. The effects of i to i 00 nM caffeine-treated rats than in those from control rats, increased prostaglandin E1 to inhibit platelet aggregation and to stimulate alpha-i adenosine receptor-mediated inhibition of lipolysis and adenylate cyclase activity in platelet membranes were also sig- of adenylate cyclase was not detected. Thus, chronic caffeine nificantly greater with caffeine-treated than with control rats. consumption causes alterations in the response of some but not These data suggest that the increased ability of NECA to inhibit all peripheral cell types to agonists of adenosine receptors. platelet aggregation after chronic caffeine ingestion was a result It is widely accepted that many of the effects of caffeine and platelet aggregation, inhibition of lipolysis, relaxation o