Hypersensitivity of diabetic human platelets to platelet activating factor.
Platelet activating factor (PAF) stimulated aggregation and [32P]-phosphatidic acid (PA) production was compared in normal and diabetic human subjects in platelet rich plasma. The concentration of PAF for half maximal (50%) aggregation of normal and diabetic platelets was 50 nM and 8 nM, respectively. PAF stimulated [32P]-PA production (a metabolite of phospholipase C pathway) was also greater in the platelets from diabetic subjects. This [32P]-PA production was inhibited by the PAF receptor antagonists SRI-63441 and SRI-63675. When the levels of glycosylated hemoglobin (HbA1c) were compared with the PAF stimulated [32P]-PA production a significant relationship was observed. These studies have demonstrated for the first time that diabetic human platelets show hypersensitivity to PAF in both aggregation and [32P]-PA production compared to normal subjects. This may be a result of some modification in phospholipid turnover mechanism and is receptor mediated. Further, the relationship of the degree of aggregation and [32P]-PA production to the level of HbA1c suggest that the insulin deficiency may contribute to these effects.
Shukla
S D
SD
Department of Pharmacology, University of Missouri School of Medicine, Columbia 65212.
Paul
A
A
Klachko
D M
DM
D001792:Blood Platelets / Q000187:drug effects; D003920:Diabetes Mellitus / Q000097:blood*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008055:Lipids / Q000097:blood; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins; D011804:Quinolines / Q000494:pharmacology; D011806:Quinolinium Compounds / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction / Q000187:drug effects
D006442:Glycated Hemoglobin; D008055:Lipids; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011804:Quinolines; D011806:Quinolinium Compounds; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C050531:SRI 63-441; C053130:SRI 63-675