title: Histamine-stimulated and GTP-binding proteins-mediated phospholipase A2 activation in rabbit platelets.
abstract: Histamine is known to be a mediator of inflammation. In order to understand the role of histamine in platelets, we have examined the effects of histamine on arachidonic acid (AA) release, cAMP accumulation, inositol trisphosphate production, and serotonin secretion. Incubation of rabbit (and human) platelets with histamine resulted in rapid increase of [3H]AA release from the platelets prelabeled with [3H]AA. The effect of histamine was blocked by the addition of H1 receptor antagonist mepyramine. Histamine did not substantially affect the cAMP content and inositol trisphosphate production. Histamine-stimulated AA release was not observed in digitonin-permeabilized platelets, whereas histamine acted synergistically with GTP or GTP analog, guanosine 5'-(3-O-thio)triphosphate. Histamine-stimulated, and GTP analog-dependent AA release was inhibited by guanosine 5'-(2-O-thio) diphosphate. The effects of three receptor stimulants, thrombin, norepinephrine, and histamine were both diminished by 1 microgram/ml of pertussis toxin treatment and by the antiserum against GTP-binding proteins (G proteins) treatment. However, the antiserum against beta gamma subunits of G proteins inhibited the histamine effect, not thrombin effect. 4 beta-Phorbol 12-myristate 13-acetate (PMA) treatment enhanced histamine-stimulated AA release and serotonin secretion but inhibited thrombin-stimulated reactions. The effect of PMA was dose dependent and was due to enhance the coupling of histamine receptors and G proteins. The results show the existence of H1 histamine receptors which couple phospholipase A2 activation via pertussis toxin-sensitive G proteins. Histamine actions differ in sensitivities to anti-beta gamma antiserum treatment and PMA treatment from thrombin actions.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Murayama
authors.forename: Y
authors.initials: Y
authors.lastname: Kajiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Nomura
mesh_terms: D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D001792:Blood Platelets / Q000201:enzymology*; D000242:Cyclic AMP / Q000097:blood; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000276:immunology / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007700:Kinetics; D009638:Norepinephrine / Q000494:pharmacology; D037342:Pertussis Toxin; D010740:Phospholipases / Q000097:blood*; D010741:Phospholipases A / Q000097:blood*; D054467:Phospholipases A2; D011817:Rabbits; D011969:Receptors, Histamine H1 / Q000502:physiology; D012701:Serotonin / Q000097:blood; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D001095:Arachidonic Acids; D007106:Immune Sera; D011969:Receptors, Histamine H1; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D016718:Arachidonic Acid; D012701:Serotonin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006632:Histamine; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D037342:Pertussis Toxin; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D013917:Thrombin; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D009638:Norepinephrine