Regulation of the receptor for platelet-activating factor on human platelets.
Human platelets possess about 300 receptors for platelet-activating factor (PAF) per cell with a Kd of about 0.2 nM. In the present study we investigated whether these receptors are subject to intracellular control mechanisms. Preincubation with the protein kinase C inhibitor staurosporine had no effect, and also agents that increase cyclic AMP failed to change the binding of [3H]PAF. The Ca(2+)-calmodulin inhibitors W-7 and sphingosine decreased PAF binding by 50-80%. Inhibition of energy metabolism induced a fall in adenylate energy charge [AEC = ([ATP] + 1/2[ADP])([ATP + ADP + AMP])] and an almost parallel decrease in specific [3H]PAF binding without changing the Kd. Restoration of the AEC restored the [3H]PAF binding. Abrupt arrest of energy metabolism during binding of [3H]PAF left the binding unchanged until the metabolic ATP level had decreased by about 90%. These data indicate that PAF receptors on human platelets are under close intracellular control, possibly via a Ca(2+)-calmodulin-dependent phosphorylation/dephosphorylation process.
Burgers
J A
JA
Department of Haematology, University Hospital Utrecht, The Netherlands.
Akkerman
J W
JW
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology; D000968:Antimycin A / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D000242:Cyclic AMP / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D010750:Phosphoproteins / Q000097:blood; D010972:Platelet Activating Factor / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011956:Receptors, Cell Surface / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D013110:Sphingosine / Q000494:pharmacology; D019311:Staurosporine; D013449:Sulfonamides / Q000494:pharmacology
D000470:Alkaloids; D002147:Calmodulin; D010750:Phosphoproteins; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013449:Sulfonamides; C039351:platelet activating factor receptor; D000244:Adenosine Diphosphate; D000968:Antimycin A; C017967:W 7; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D000242:Cyclic AMP; D011493:Protein Kinase C; D019311:Staurosporine; D013110:Sphingosine