title: GDP beta S enhances the activation of phospholipase C caused by thrombin in human platelets: evidence for involvement of an inhibitory GTP-binding protein.
abstract: Guanosine 5'-O-thiotriphosphate (GTP gamma S) and thrombin stimulate the activity of phospholipase C in platelets that have been permeabilized with saponin and whose inositol phospholipids have been prelabeled with [3H]inositol. Ca2+ has opposite effects on the formation of [3H]inositol phosphates induced by thrombin or GTP gamma S. While the action of GTP gamma S on the formation of [3H]inositol phosphates is inhibited by Ca2+, action of thrombin is stimulated by Ca2+. Guanosine 5'-O-(2-thiodiphosphate) (GDP beta S), which inhibits the function of GTP-binding proteins, also inhibits the effect of GTP gamma S on phospholipase C stimulation but, surprisingly, increases the effect of thrombin. Ca2+ increases the inhibitory effect of GDP beta S on GTP gamma S activation of phospholipase C, but Ca2+ further enhances the stimulatory effect of GDP beta S on the thrombin activation of phospholipase C. This indicates that two mechanisms are responsible for the activation of phospholipase C in platelets. A GTP-binding protein is responsible for regulation of phospholipase C induced by GTP gamma S, while the effect of thrombin on the stimulation of phospholipase C is independent of GTP-binding proteins. However, the effect of thrombin may be modulated by the action of an inhibitory GTP-binding protein.
mesh_terms: D001792:Blood Platelets / Q000201:enzymology*; D002118:Calcium / Q000494:pharmacology; D002463:Cell Membrane Permeability; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000097:blood*; D006150:Guanine Nucleotides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000097:blood; D007700:Kinetics; D012503:Saponins / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology*; D013917:Thrombin / Q000502:physiology*; D014316:Tritium; D010738:Type C Phospholipases / Q000097:blood*
chemical_list: D006150:Guanine Nucleotides; D007295:Inositol Phosphates; D012503:Saponins; D013873:Thionucleotides; D014316:Tritium; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D007294:Inositol; C023427:guanosine 5'-O-(2-thiodiphosphate); D006160:Guanosine Triphosphate; D010738:Type C Phospholipases; D013917:Thrombin; D019204:GTP-Binding Proteins; D002118:Calcium