Premium
Caffeine Enhances ATP Release from Erythrocytes: Consequences for Peripheral Vascular Perfusion
Author(s) -
Ellsworth Mary L.,
Chrzaszcz MaryAnn,
O'Keefe Emily,
Achilleus David,
Bowles Elizabeth,
Sprague Randy S.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a479-d
Subject(s) - caffeine , xanthine , perfusion , chemistry , adenosine , adenosine triphosphate , biochemistry , intracellular , pharmacology , theophylline , phosphodiesterase , medicine , endocrinology , biology , enzyme
ATP, a regulator of microvascular perfusion, is released from erythrocytes (RBCs) in response to desaturation of the hemoglobin molecule. Evidence exists to suggest that under pathologic conditions, such as diabetes and sepsis, ATP release from RBCs is impaired which contributes to the concomitant impairment in microvascular perfusion generally associated with these diseases. Caffeine, a widely consumed methylated xanthine, inhibits some forms of cyclic nucleotide phosphodiesterases (CNPs) decreasing the hydrolysis of cAMP resulting in an elevation of its intracellular levels. Since the signal transduction pathway for ATP release from RBCs requires an elevation of cAMP, it is reasonable to assume that a cause and effect relationship could exist between caffeine and erythrocyte ATP release which would help explain the abundant anecdotal evidence indicating that caffeine consumption has a beneficial effect on the well being of patients. To evaluate the impact of caffeine on ATP release we used an in vitro system and rabbit RBCs and exposed them for 1 minute to a level of caffeine which would be expected in an individual who had consumed 1–2 cups of coffee (70 μM). We found that this amount of caffeine increased the release of ATP from red blood cells by almost 70% resulting in levels which were not different from those following exposure to low PO2 in the absence of caffeine. In addition, we observed that this amount of caffeine induced a significant 22% increase in levels of intraerythrocytic cAMP supporting the mechanism of caffeine's enhancement of ATP release. This result provides further evidence for the importance of the RBC in vascular control and evidence that its activity can be manipulated by altering the production and/or hydrolysis of cAMP. (NIH HL‐56249)