Energy production and utilization by human platelets in the presence of some guanidines and phenols (uremic toxins) that inhibit aggregation.
Platelet aggregation induced by ADP can be inhibited by plasma from uremic patients or by toxins isolated from their plasma, e.g. guanidinosuccinic acid, methylguanidine, phenol and hydroxyphenylacetic acids. Since these chemical substances can interfere with energy metabolism in tissues other than platelets and since ATP production is needed for ADP-induced aggregation, alterations in platelet energy metabolism could underlie excessive bleeding in uremic patients. Platelets incubated with idioacetate and deprived of anaerobic glycolysis produced the same quantity of ATP through respiration in the presence of all the uremic toxins studied as in their absence. Similarly, platelets incubated with cyanide and deprived of the oxidative pathway utilized anaerobic glycolysis to produce normal quantities of ATP in the presence of all the uremic toxins. The utilization of ATP, as indicated by active transmembrane potassium transport, was also unaffected by the above listed guanidines and phenols. It is concluded that the in vitro inhibition of ADP-induced platelet aggregation by the guanidines and phenols studied is not due to inhibition of production or utilization of ATP.
D000255:Adenosine Triphosphate / Q000378:metabolism; D001693:Biological Transport, Active / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D006019:Glycolysis / Q000187:drug effects; D006146:Guanidines / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007773:Lactates / Q000378:metabolism; D008760:Methylguanidine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D010648:Phenylacetates / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology; D014511:Uremia / Q000097:blood*
D006146:Guanidines; D007773:Lactates; D010636:Phenols; D010648:Phenylacetates; D014475:Uncoupling Agents; D008760:Methylguanidine; D000255:Adenosine Triphosphate; D011188:Potassium