Modulation of 3′,5′-cyclic AMP homeostasis in human platelets by coffee and individual coffee constituents

Abstract

3 0 ,5 0 -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.

A Review of Natural Stimulant and Non‐stimulant Thermogenic Agents

“…In vascular smooth muscle cells, caffeine acts predominantly as a competitive inhibitor of the enzyme phosphodiesterase, which is responsible for the breakdown of 3 ,5 -cAMP. cAMP is one of the most important second messengers in mammalian cells and is responsible for diverse signaling responses including those responsible for energetic status (AMP/ATP ratio) and the effects of caffeine and coffee (Montoya et al, 2014;Nunes et al, 2014).…”

Alkylpyrazines from Coffee are Extensively Metabolized to Pyrazine Carboxylic Acids in the Human Body

“…A major metabolite of ligustrazine in human urine was 3,5,6‐trimethylpyrazine‐2‐carboxylic acid . We were able to show that alkylpyrazines from coffee inhibited 3’5’‐cyclic AMP phosphodiesterase in vitro . Additionally, in a 7‐week human intervention study, the effects of coffee constituents on platelet phosphodiesterase and the homeostasis of intracellular cAMP were tested.…”

Aus den Hochschulstandorten

“…Eine Korrelation dieser Daten mit dem Energiehaushalt der Zellen konnte bestätigt werden. So war die intrazelluläre Konzentration des Signalmoleküls cyclisches Adenosinmonophosphat ( cAMP ) erhöht und die Aktivität des regulatorischen cAMP-abbauenden Enzyms ( Phosphodiesterease, PDE ) in den Thrombozyten der Probanden reduziert [31,32]. Eine DNA-protektive Wirkung durch Kaffeekonsum ist seit einigen Jahren bekannt [33].…”