Effect of pyridoxal 5'-phosphate (PALP) on human platelet aggregation, dense granule release and thromboxane B2 generation--role of Schiff base formation.
Pyridoxal 5'-phosphate (PALP) inhibited ADP, thrombin, adrenaline, PAF and AA induced aggregation and 14C-5HT release. Thromboxane B2 (TxB2) generation induced by all the above agents except AA was also inhibited indicating that PALP may be inhibiting AA release via phospholipase A2 activation rather than AA metabolism. PALP inhibited ristocetin induced aggregation in PRP and agglutination in formaldehyde-treated washed platelets (FWP). Inhibition of ADP, adrenaline, PAF and AA-induced aggregation and 14C-5HT release by PALP was found in resuspended platelets pretreated with PALP and sodium borohydride suggesting that inhibition was mediated by Schiff base formation with platelet surface amino groups. Irreversible fixation of PALP to the platelet membrane by borohydride reduction also inhibited thrombin induced 14C-5HT release and TxB2 generation but no thrombin induced primary aggregation or ristocetin induced agglutination in FWP. This suggests that PALP may interact with specific glycoproteins on the platelet membrane involved in ADP, adrenaline and PAF induced primary aggregation and that PALP could be inhibiting ristocetin induced agglutination by direct interaction with ristocetin or F VIII RCoF.
D000527:Alprostadil; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D003594:Cytoplasmic Granules / Q000378:metabolism*; D005557:Formaldehyde / Q000494:pharmacology; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D011458:Prostaglandins E / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000494:pharmacology*; D012310:Ristocetin / Q000494:pharmacology; D012545:Schiff Bases / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D011458:Prostaglandins E; D012545:Schiff Bases; D013931:Thromboxanes; D012310:Ristocetin; D005557:Formaldehyde; D012701:Serotonin; D013929:Thromboxane B2; D011732:Pyridoxal Phosphate; D000527:Alprostadil