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Caffeine alters A2A adenosine receptors and their function in human platelets
K Varani1, F Portaluppi, S Merighi
1Department of Clinical and Experimental Medicine, University of Ferrara, San Raffaele Science Park, Milan, Italy.
Circulation
|May 20, 1999
Summary
Repeated caffeine intake upregulates human platelet A2A adenosine receptors. This leads to increased sensitivity in platelet responses, such as cAMP accumulation and reduced aggregation, following A2A receptor stimulation.
Area of Science:
- Pharmacology
- Molecular Biology
- Cardiovascular Research
Background:
- Caffeine primarily acts by blocking adenosine receptors, which include subtypes A1, A2A, A2B, and A3.
- Adenosine receptors play crucial roles in various physiological processes, including platelet function.
Purpose of the Study:
- To investigate whether chronic caffeine consumption upregulates A2A adenosine receptors in human platelets.
- To determine if this upregulation is associated with enhanced platelet sensitivity to A2A receptor stimulation.
Main Methods:
- Human volunteers received 750 mg/d of caffeine for one week.
- Platelets were collected at baseline (abstinence) and 12 and 60 hours post-caffeine withdrawal.
- A2A receptor density was measured using radioligand binding ([3H]SCH 58261).
- Platelet responses, including cAMP accumulation and aggregation, were assessed following stimulation with an A2A receptor agonist (HE-NECA).
Main Results:
- Chronic caffeine intake significantly increased the density (Bmax) of A2A receptors in human platelets.
- Platelets from caffeine-withdrawn volunteers showed increased sensitivity to the A2A receptor agonist HE-NECA.
- This sensitization was evidenced by a lower concentration required for HE-NECA to increase cAMP accumulation (reduced EC50) and inhibit platelet aggregation (reduced IC50).
Conclusions:
- Chronic caffeine consumption leads to an upregulation of A2A adenosine receptors on human platelets.
- This upregulation is accompanied by enhanced platelet responsiveness to A2A receptor agonist stimulation, indicating functional sensitization.
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