title: Modulation of 3',5'-cyclic AMP homeostasis in human platelets by coffee and individual coffee constituents.
abstract: 3',5'-Cyclic AMP (cAMP) is one of the most important second messengers in mammalian cells, mediating a multitude of diverse cellular signalling responses. Its homeostasis is primarily regulated by adenylate cyclases and phosphodiesterases (PDE), the activities of which are partially dependent on the downstream events of adenosine receptor signalling. The present study was conducted to determine whether coffee constituents other than caffeine can influence the homeostasis of intracellular cAMP in vitro and in vivo by evaluating the effects of selected constituents present in coffee, coffee brews and coffee extracts on platelet PDE activity. In addition, to evaluate the potential effects of these constituents on platelet cAMP concentrations and PDE activity in humans, a 7-week pilot intervention study with eight subjects was conducted. The subjects consumed a regular commercial coffee and a low-caffeine coffee at a rate of 750 ml/d for 2 weeks each. The in vivo results revealed a highly significant inhibition of PDE activity (P< 0·001) after coffee intervention that was not directly dependent on the caffeine content of coffee. Although our in vitro and in vivo findings suggest that caffeine plays some role in the modulation of platelet cAMP status, other natural and roasting-associated compounds such as pyrazines and other currently unidentified species also appear to contribute significantly. In conclusion, moderate consumption of coffee can modulate platelet PDE activity and cAMP concentrations in humans, which may contribute to the putative beneficial health effects of coffee. Further detailed mechanistic investigations will be required to substantiate these beneficial effects and to elucidate the underlying mechanisms.
authors.affiliation: Division of Food Chemistry and Toxicology, Molecular Nutrition, Department of Chemistry, University of Kaiserslautern,Erwin-Schroedinger-Strasse 52,67663Kaiserslautern,Germany.
authors.forename: Gina A
authors.initials: GA
authors.lastname: Montoya
authors.affiliation: Division of Food Chemistry and Toxicology, Molecular Nutrition, Department of Chemistry, University of Kaiserslautern,Erwin-Schroedinger-Strasse 52,67663Kaiserslautern,Germany.
authors.forename: Tamara
authors.initials: T
authors.lastname: Bakuradze
authors.affiliation: Division of Food Chemistry and Toxicology, Molecular Nutrition, Department of Chemistry, University of Kaiserslautern,Erwin-Schroedinger-Strasse 52,67663Kaiserslautern,Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Eirich
authors.affiliation: Division of Food Chemistry and Toxicology, Molecular Nutrition, Department of Chemistry, University of Kaiserslautern,Erwin-Schroedinger-Strasse 52,67663Kaiserslautern,Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Erk
authors.affiliation: Division of Food Chemistry and Toxicology, Molecular Nutrition, Department of Chemistry, University of Kaiserslautern,Erwin-Schroedinger-Strasse 52,67663Kaiserslautern,Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Baum
authors.affiliation: Division of Food Chemistry and Toxicology, Molecular Nutrition, Department of Chemistry, University of Kaiserslautern,Erwin-Schroedinger-Strasse 52,67663Kaiserslautern,Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Habermeyer
authors.affiliation: Division of Food Chemistry and Toxicology, Molecular Nutrition, Department of Chemistry, University of Kaiserslautern,Erwin-Schroedinger-Strasse 52,67663Kaiserslautern,Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Eisenbrand
authors.affiliation: Division of Food Chemistry and Toxicology, Molecular Nutrition, Department of Chemistry, University of Kaiserslautern,Erwin-Schroedinger-Strasse 52,67663Kaiserslautern,Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Richling
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000097:blood; D000241:Adenosine / Q000097:blood; D000243:Adenosine Deaminase / Q000097:blood; D000328:Adult; D001792:Blood Platelets / Q000737:chemistry*; D002110:Caffeine / Q000032:analysis / Q000494:pharmacology*; D003069:Coffee / Q000737:chemistry*; D000242:Cyclic AMP / Q000097:blood*; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D003069:Coffee; D010726:Phosphodiesterase Inhibitors; D011719:Pyrazines; D002110:Caffeine; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000243:Adenosine Deaminase; D000241:Adenosine