Murayama T, Kajiyama Y, Nomura Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
J Biol Chem. 1990 Mar 15;265(8):4290-5.
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.
已知组胺是炎症介质。为了解组胺在血小板中的作用，我们研究了组胺对花生四烯酸（AA）释放、环磷酸腺苷（cAMP）积累、三磷酸肌醇生成以及5-羟色胺分泌的影响。用组胺孵育兔（和人）血小板，导致预先用[3H]AA标记的血小板中[3H]AA释放迅速增加。加入H1受体拮抗剂美吡拉敏可阻断组胺的作用。组胺对cAMP含量和三磷酸肌醇生成没有实质性影响。在洋地黄皂苷通透的血小板中未观察到组胺刺激的AA释放，而组胺与鸟苷三磷酸（GTP）或GTP类似物5'-（3-O-硫代）三磷酸鸟苷协同作用。5'-（2-O-硫代）二磷酸鸟苷可抑制组胺刺激的、GTP类似物依赖性的AA释放。三种受体刺激剂凝血酶、去甲肾上腺素和组胺的作用，在1微克/毫升百日咳毒素处理和抗GTP结合蛋白（G蛋白）抗血清处理后均减弱。然而，抗G蛋白βγ亚基的抗血清抑制组胺作用，而非凝血酶作用。4β-佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）处理增强组胺刺激的AA释放和5-羟色胺分泌，但抑制凝血酶刺激的反应。PMA的作用呈剂量依赖性，是由于增强了组胺受体与G蛋白的偶联。结果表明存在通过百日咳毒素敏感的G蛋白偶联磷脂酶A2激活的H1组胺受体。组胺作用在对抗βγ抗血清处理和PMA处理的敏感性方面与凝血酶作用不同。
