The effect of amphiphilic phenylalkyl derivatives on platelet energy metabolism. Stimulation of glycolysis through activation of membrane ATPase.
In order to obtain information about the target of membrane-active inhibitors of platelet aggregation two phenylalkanoles and two phenylalkylamines were examined with respect to their influence on membrane ATPase and energy metabolism. The phenylalkanoles, 2-phenylethanol and 3-phenylpropanol, strongly enhanced the liberation in washed platelets of inorganic phosphate (Pi) from endogenous substrate or added ATP. A simultaneous decrease was found in the ATP/ADP ratio while glucose uptake, glycogen utilization and lactate formation increased. The effects of 2-phenylethanol and 3-phenylpropanol on Pi liberation and ATP/ADP ratio were detectable only with starving platelets; the stimulation of glycolysis could also be seen when glucose was added. It is concluded that presence of glucose enabled the platelets to reincorporate additionally liberated Pi into their ATP pool by virtue of the higher metabolic rate. The data suggest that a membrane-ATPase, possibly thrombosthenin ATPase, is the target of the phenylalkanoles. The phenylalkylamines, 2-phenylethylamine and 4-phenylbutylamine, appeared to inhibit Pi liberation and energy metabolism. Hence the aggregation inhibition produced by amphiphilic phenylalkylamines and phenylalkanoles is not due to a uniform metabolic effect of both classes of derivatives.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000097:blood*; D000255:Adenosine Triphosphate / Q000097:blood; D000328:Adult; D000473:Alkanes / Q000494:pharmacology; D001555:Benzene Derivatives / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D004734:Energy Metabolism / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D010101:Oxygen Consumption / Q000187:drug effects; D010710:Phosphates / Q000097:blood; D013268:Stimulation, Chemical
D000473:Alkanes; D001555:Benzene Derivatives; D010710:Phosphates; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases