Platelet-activating factor modulates microvascular transport by stimulation of protein kinase C.
Platelet-activating factor modulates microvascular transport by stimulation of protein kinase C.
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血小板激活因子通过刺激蛋白激酶 C 调节微血管运输。
DOI：
10.1152/ajpheart.1994.266.3.h1214
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Durán,WN
中科院分区：
文献类型：
--
作者：
Kobayashi,I;Kim,D;Hobson2nd,RW;Durán,WN
为了探讨蛋白激酶C在血小板活化因子刺激的微血管反应中的可能作用，在金黄地鼠颊囊局部应用蛋白激酶C抑制剂鞘氨醇(Sph)、1-(5-isoquino-linylsulfonyl)-3-methylpiperazine(iso H-7)和Calphostin C，并观察了血小板活化因子对微血管通透性和微动脉收缩的影响。10(-6)M SPH、10(-5)M SPH或10(-10)M isoH-7可显著降低10(-7)M PAF诱导的荧光素异硫氰酸盐-葡聚糖150清除量的增加(分别为2,677.3+/-397.3、2,985.3+/-350.7和2,689.3+/-256.0 vs.4,784.0+/-474.7 nL.60min-1.g-1)。在10(-7)M时，Calphostin C可减弱10(-8)M PAF诱导的清除量增加(2,156.9+/-353.3比3,841.6+/-260.9 nL.60min-1.g-1)。通过积分光强度(IOI)测量通透性的变化。10(-6)M SPH、10(-5)M SPH或10(-10)M iso H-7可减弱10(-7)M PAF诱导的IOI最大增量(分别为2,024.0+/-364.4、1,690.0+/-525.2和2,432.8+/-655.3比4,255.9+/-695.6 U)。佛波醇二丁酸酯直接刺激PKC可剂量依赖性地增加清除量。同样地，佛波醇肉豆蔻酸酯激活PKC可增加IOI值。PKC抑制剂不能阻断PAF引起的小动脉收缩。我们的结果提示，PKC是参与PAF调节微血管通透性的生化途径，而不是微动脉收缩。
To investigate the possible involvement of protein kinase C (PKC) in platelet-activating factor (PAF)-stimulated microvascular responses, PKC inhibitors, sphingosine (SPH), 1-(5-isoquino-linylsulfonyl)-3-methylpiperazine (iso H-7), and calphostin C, were applied topically to the hamster cheek pouch, and PAF-elicited changes in microvascular permselectivity and arteriolar constriction were evaluated. Pretreatment with 10(-6) M SPH, 10(-5) M SPH, or 10(-10) M iso H-7 significantly reduced 10(-7) M PAF-induced increase in fluorescein isothiocyanate-Dextran 150 clearance (2,677.3 +/- 397.3, 2,985.3 +/- 350.7, and 2,689.3 +/- 256.0 vs. 4,784.0 +/- 474.7 nl.60 min-1.g-1, respectively). Calphostin C at 10(-7) M attenuated 10(-8) M PAF-induced increase in clearance (2,156.9 +/- 353.3 vs. 3,841.6 +/- 260.9 nl.60 min-1.g-1). Permeability changes were also measured by integrated optical intensity (IOI). Pretreatment with 10(-6) M SPH, 10(-5) M SPH, or 10(-10) M iso H-7 attenuated the maximal increment in IOI induced by 10(-7) M PAF (2,024.0 +/- 364.4, 1,690.0 +/- 525.2, and 2,432.8 +/- 655.3 vs. 4,255.9 +/- 695.6 U, respectively). Direct stimulation of PKC by phorbol dibutyrate increased clearance in dose-dependent fashion. Similarly, activation of PKC with phorbol myristate acetate increased IOI values. The PAF-induced arteriolar constriction was not blocked by the PKC inhibitors. Our results suggest that PKC represents a biochemical pathway involved in the PAF modulation of microvascular permeability but not of arteriolar constriction.