Failure of methylhistidines to inhibit platelet aggregation at concentrations found in uremic plasma.
Methylhistidines are among the amino acids which are present in increased concentrations in the plasma of severely uremic patients who may have a hemorrhagic diathesis. Histidine contains an imidazole ring, and our previous work has shown inhibition of collagen-induced platelet aggregation by imidazole in concentrations as low as 0.5 mM. Collagen-induced, adenosine diphosphate-induced, and norepinephrine-induced platelet aggregation were tested in platelet-rich plasma by a turbidimetric technique after incubation of the plasma with varying concentrations of the methylhistidines for 1 hour. Platelet aggregation was unaffected by methylhistidine concentrations up to 0.6 mM. Only norepinephrine-induced platelet aggregation was slightly inhibited at a concentration of 4.7 (mM far higher than found in uremic patients). The imidazole ring as a portion of the methylhistidine molecule appears to have lost much of its effect on platelet aggregation.
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000328:Adult; D003094:Collagen / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006474:Hemorrhagic Disorders / Q000097:blood; D006639:Histidine / Q000031:analogs & derivatives*; D006801:Humans; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D008762:Methylhistidines / Q000097:blood / Q000494:pharmacology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014511:Uremia / Q000097:blood*
D007093:Imidazoles; D008762:Methylhistidines; D006639:Histidine; D000244:Adenosine Diphosphate; D003094:Collagen; D009638:Norepinephrine