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(Circulation. 2000;102:285.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Dose and Time Effects of Caffeine Intake on Human Platelet Adenosine A_2A Receptors

Functional and Biochemical Aspects

Katia Varani, PhD; Francesco Portaluppi, MD; Stefania Gessi, PhD; Stefania Merighi, MSc; Ennio Ongini, PhD; Luiz Belardinelli, MD; Pier Andrea Borea, PhD

From the Department of Clinical and Experimental Medicine, University of Ferrara (K.V., F.P., S.G., S.M., P.A.B.), and Schering-Plough Research Institute, Milan (E.O.), Italy; and Department of Medicine, Division of Cardiology, University of Florida, Gainesville (L.B.).

Correspondence to Prof Pier Andrea Borea, Department of Clinical and Experimental Medicine, University of Ferrara, Via Fossato di Mortara 17-19, 44100 Ferrara, Italy. E-mail bpa{at}dns.unife.it

Background—We determined whether repeated caffeine administration at different dosages and for different periods of time (400 or 600 mg/d for 1 week or 400 mg/d for 2 weeks) upregulates human platelet adenosine A_2A receptors and is accompanied by increases in cAMP accumulation and decreases in aggregation and calcium levels after stimulation of A_2A receptors by the selective 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 and at 12, 60, and 108 hours after the last dose of caffeine. The lowest dose of caffeine, when given for only 7 days, had no effect. Increasing the total dose, either by giving 400 mg/d for 14 days or giving 600 mg/d, resulted in binding assays performed with the adenosine A_2A receptor radioligand [³H]SCH 58261 [5-amino-7(phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine], in the upregulation of A_2A receptors. Moreover, the potency of HE-NECA to produce antiaggregatory effects, a rise in cAMP accumulation, 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.

Key Words: adenosine • receptors • caffeine • platelets

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