High- and low-affinity receptors regulate platelet responses to phorbol diesters and teleocidin.
We examined binding of 3H-phorbol dibutyrate (3H-PDBu) to gel filtered human platelets (GFP) and discovered that GFP possess two classes of receptors for phorbol diesters (PDE). High-affinity (HA) receptors, approximately 5000/GFP, bound 3H-PDBu with an apparent dissociation constant (KD) of approximately 12 nM. Low-affinity receptors were approximately 5 times more numerous (2.4 X 10(4)/GFP) and had a 10-fold lower affinity for 3H-PDBu (apparent KD = 115 nM). The potencies of phorbol myristate acetate (PMA) and PDBu paralleled their binding affinities to the PDE receptors. Teleocidin (Tel), although structurally distinct from PDE, competed with 3H-PDBu for its HA-receptors (KI Tel = 1.9 nM). Binding of PDE to HA- or LA- receptors was rapid, reversible, saturable and stereospecific. The HA- and LA-receptors modulated different platelet responses. HA-receptors regulated the secretion of beta-thromboglobulin from alpha-granules and the release of N-acetyl-beta-D-hexosaminidases from lysosomes. LA-receptors mediated both platelet aggregation and the release of serotonin from dense granules. This is the first demonstration of two physiologically active classes of PDE/Tel receptors in human platelets, and demonstrates that particular platelet responses may be directed by distinct classes of receptors for specific agonists.
D001667:Binding, Competitive; D001792:Blood Platelets / Q000187:drug effects* / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D002850:Chromatography, Gel / Q000379:methods; D006801:Humans; D008235:Lyngbya Toxins / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000378:metabolism / Q000494:pharmacology*; D011493:Protein Kinase C; D011956:Receptors, Cell Surface / Q000502:physiology*; D011955:Receptors, Drug; D011971:Receptors, Immunologic / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D001620:beta-Thromboglobulin / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D008235:Lyngbya Toxins; D010703:Phorbol Esters; D011956:Receptors, Cell Surface; D011955:Receptors, Drug; D011971:Receptors, Immunologic; D001620:beta-Thromboglobulin; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; C022176:teleocidins; D012701:Serotonin; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate