Schramm C M, Grunstein M M
Joseph Stokes, Jr., Research Institute, Department of Pediatrics, Children's Hospital of Philadelphia, Pennsylvania.
J Appl Physiol (1985). 1989 Apr;66(4):1935-41. doi: 10.1152/jappl.1989.66.4.1935.
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)
为阐明蛋白激酶C（PK - C）在调节气道收缩性中的作用，分别评估了佛波酯、12 - 脱氧佛波醇13 - 异丁酸酯（DPB）和佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）以及二酰基甘油类似物1 - 油酰基 - 2 - 乙酰基 - 外消旋甘油（OAG）激活PK - C对离体兔气管平滑肌（TSM）节段的影响。后几种药物产生了双重且相反的收缩效应，其中DPB最为有效。较低剂量的DPB（小于或等于10⁻⁶ M）可使未处理的TSM以及用乙酰甲胆碱预收缩至半数最大张力的TSM的等长张力显著增加。这些增强的TSM收缩被钙通道阻滞剂硝苯地平（10⁻⁴ M）和地尔硫䓬（10⁻⁵ M）抑制。相反，较高剂量的DPB（大于或等于10⁻⁶ M）诱导气道舒张，而哇巴因（5×10⁻⁶ M）预抑制电生性钠钾泵或无钾缓冲液可消除这种舒张作用。实际上，在单独的实验中发现DPB（10⁻⁷ M）可显著增强钠钾泵的功能活性，这种效应的发生与用氨氯地平（10⁻⁴ M）抑制钠氢交换或用硝苯地平（10⁻⁴ M）抑制细胞外钙内流无关。（摘要截短于250字）
