Receptor-regulated formation of GTP[gamma S] with subsequent persistent Gs-protein activation in membranes of human platelets.
Preincubation of human platelet membranes with the ATP analog ATP[gamma S] led to persistent adenylate cyclase activation. This stimulation was increased by copreincubation with PGE1 and obliterated by removing endogenous GDP by the NTP-regenerating system, creatine phosphate plus creatine kinase. PGE1 partially reversed the action of the regenerating system. Control formation of GTP[gamma S] from ATP[gamma S] and GDP in platelet membranes was apparently not stimulated by PGE1. In contrast, in the presence of creatine phosphate plus creatine kinase, which prevented formation of GTP[gamma S], PGE1 stimulated formation of this GTP analog, by partially reversing the action of the NTP-regenerating system. The data indicate that GTP[gamma S] can be formed by a membrane-associated nucleoside diphosphokinase from ATP[gamma S] and GDP, resulting in persistent Gs-protein activation, and that this process can be stimulated by an agonist-activated receptor.
Wieland
T
T
Pharmakologisches Institut der Universität Heidelberg, FRG.
Jakobs
K H
KH
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000097:blood; D000527:Alprostadil / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000097:blood*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006153:Guanosine Diphosphate / Q000097:blood / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000097:blood; D006801:Humans; D008274:Magnesium / Q000494:pharmacology; D015636:Magnesium Chloride; D010725:Phosphocreatine / Q000378:metabolism; D013873:Thionucleotides / Q000097:blood*
D013873:Thionucleotides; D010725:Phosphocreatine; D015636:Magnesium Chloride; D006153:Guanosine Diphosphate; C022571:adenosine 5'-O-(3-thiotriphosphate); D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000527:Alprostadil; D008274:Magnesium