Mechanisms of protein kinase C regulation of airway contractility.
Mechanisms of protein kinase C regulation of airway contractility.
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蛋白激酶 C 调节气道收缩力的机制。
DOI：
10.1152/jappl.1989.66.4.1935
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Grunstein,MM
中科院分区：
文献类型：
--
作者：
Schramm,CM;Grunstein,MM
为了阐明蛋白激酶C （PK-C）在调节气道收缩性中的作用，在离体家兔气管平滑肌（TSM）节段中，分别评价了蛋白激酶C与酚酯、12-脱氧酚13-异丁酸酯（DPB）和12-肉豆蔻酸13-乙酸酯（PMA）以及二酰基甘油类似物1-油基-2-乙酸酯-丙三醇（OAG）的激活作用。后一种药物产生双重和相反的收缩作用，其中DPB是最有效的。较低剂量的DPB（小于或等于10(-6)M）在未治疗的TSM和经甲胆碱预收缩的TSM中均引起等长张力的显著增加。这些增强的TSM收缩被Ca2+通道阻滞剂硝苯地平（10(-4)M）和地尔硫卓（10(-5)M）所抑制。相比之下，高剂量的DPB（大于或等于10(-6)M）诱导气道松弛，这是通过用瓦巴因（5 × 10(-6) M）或无K+缓冲液预抑制电致Na+-K+泵而消融的。事实上，在单独的实验中发现DPB （10(-7) M）可以显著增强Na+-K+泵的功能活性，这种作用独立于与阿米洛利（10(-4)M）或硝苯地平（10(-4)M）抑制Na+-H+交换或细胞外Ca2+内流。
To elucidate the role of protein kinase C (PK-C) in regulating airway contractility, the effects of PK-C activation with phorbol esters, 12-deoxyphorbol 13-isobutyrate (DPB), and phorbol 12-myristate 13-acetate (PMA), and with the diacylglycerol analogue 1-oleoyl-2-acetate-rac-glycerol (OAG) were separately evaluated in isolated rabbit tracheal smooth muscle (TSM) segments. The latter agents produced dual and opposing contractile effects, with DPB being the most potent. Lower doses of DPB (less than or equal to 10(-6) M) elicited significant increases in isometric tension in both untreated TSM, as well as in TSM half-maximally precontracted with methacholine. These potentiated TSM contractions were inhibited by the Ca2+ channel blockers, nifedipine (10(-4) M) and diltiazem (10(-5) M). In contrast, higher doses of DPB (greater than or equal to 10(-6) M) induced airway relaxation, which was ablated by preinhibition of the electrogenic Na+-K+ pump with ouabain (5 x 10(-6) M) or K+-free buffer. Indeed, in separate experiments DPB (10(-7) M) was found to significantly potentiate the functional activity of the Na+-K+ pump, an effect occurring independent of inhibition of Na+-H+ exchange with amiloride (10(-4) M) or extracellular Ca2+ influx with nifedipine (10(-4) M).(ABSTRACT TRUNCATED AT 250 WORDS)