Dose and time effects of caffeine intake on human platelet adenosine A(2A)receptors - Functional and biochemical aspects

Background-We determined whether repeated caffeine administration at differ ent dosages and for different periods of time (400 or 600 mg/d for 1 week o r 400 mg/d for 2 weeks) upregulates human platelet adenosine A,, receptors and is accompanied by increases in cAMP accumulation and decreases in aggre gation and calcium levels after stimulation of A,, receptors by the selecti ve agonist 2-hexynyl-5'-N-ethylcarboxamidoadenosine (HE-NECA). Methods and Results-Platelets were obtained from peripheral venous blood of 45 healthy human volunteers at the end of 2 weeks of caffeine abstinence a nd at 12, 60, and 108 hours after the last dose of caffeine. The lowest dos e of caffeine, when given for only 7 days, had no effect. Increasing the to tal dose, either by giving 400 mg/d for 14 days or giving 600 mg/d, resulte d in binding assays performed with the adenosine A, receptor radioligand [H -3]SCH 58261 [5-amino-7(phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-tria zolo[1,5-c]pyrimidine], in the upregulation of A, receptors. Moreover, the potency of HE-NECA to produce antiaggregatory effects, a rise in cAMP accum ulation, and a decrease in calcium levels was significantly increased. Conclusions-Chronic caffeine intake can lead to upregulation of adenosine A (2A) receptors, which is accompanied by sensitization, in a time- and dose- dependent manner, to the actions of the agonist HE-NECA.