Avdonin P V, Svitina-Ulitina I V, Tkachuk V A
Institute of Experimental Cardiology, Academy of Medical Sciences, Moscow, USSR.
J Mol Cell Cardiol. 1989 Feb;21 Suppl 1:139-43. doi: 10.1016/0022-2828(89)90849-3.
Incubation of human platelets with protein kinase C activator 4 beta-phorbol-12 beta-myristate-13 alpha-acetate (PMA) abolished stimulation of membrane high-affinity GTPase by platelet-activating factor (PAF). GTPase stimulation by epinephrine decreased by 30%, while the prostaglandin E1 (PGE1) effect was unchanged. Basal GTPase activity (22.4 +/- 1.1 pmol Pi/min per mg protein) was not affected by PMA. Therefore, a study was performed of the effect of endogenous protein kinase C activation on adenylate cyclase regulation by agonists. PMA pretreatment completely suppressed PAF inhibition of basal adenylate cyclase activity but hardly influenced the inhibition by PAF of forskolin-stimulated activity. Adenylate cyclase inhibition by epinephrine in the presence of propranolol was not suppressed completely after platelet incubation with PMA. Epinephrine effects on basal and forskolin-stimulated activities decreased equally. Platelet pretreatment with PMA increased PGE1-stimulated activity by abolishing the inhibitory effect of high GTP concentrations. These studies indicate that protein kinase C selectively inhibits PAF effects, presumably by inactivating a GTP-binding protein coupled with PAF receptors.
用人血小板与蛋白激酶C激活剂4β-佛波醇-12β-肉豆蔻酸酯-13α-乙酸酯（PMA）共同孵育，可消除血小板活化因子（PAF）对膜高亲和力GTP酶的刺激作用。肾上腺素对GTP酶的刺激作用降低了30%，而前列腺素E1（PGE1）的作用未变。基础GTP酶活性（每毫克蛋白质22.4±1.1皮摩尔无机磷/分钟）不受PMA影响。因此，开展了一项关于内源性蛋白激酶C激活对激动剂调节腺苷酸环化酶作用的研究。PMA预处理完全抑制了PAF对基础腺苷酸环化酶活性的抑制作用，但几乎不影响PAF对福斯高林刺激活性的抑制作用。血小板与PMA孵育后，在普萘洛尔存在的情况下，肾上腺素对腺苷酸环化酶的抑制作用并未被完全抑制。肾上腺素对基础活性和福斯高林刺激活性的作用同等程度降低。用PMA预处理血小板可通过消除高GTP浓度的抑制作用来增加PGE1刺激的活性。这些研究表明，蛋白激酶C选择性抑制PAF的作用，可能是通过使与PAF受体偶联的GTP结合蛋白失活来实现的。
