内皮素诱导兔肺静脉收缩中的信号转导

Signal transduction in endothelin-induced contraction of rabbit pulmonary vein.

作者信息

Steffan M, Russell J A

机构信息

Department of Physiology, State University of New York, Buffalo 14214.

出版信息

Pulm Pharmacol. 1990;3(1):1-7. doi: 10.1016/0952-0600(90)90002-z.

DOI:10.1016/0952-0600(90)90002-z

PMID:2135207

Abstract

The effect of porcine endothelin (endothelin 1) on rings of isolated rabbit pulmonary vein was studied using tissue bath techniques. Endothelin was found to be a potent constrictor of these vessels, producing concentration-dependent contractions with an EC50 value of 3.2 +/- 0.6 x 10(-9) M. Contractions were not significantly affected by the Ca2+ channel antagonists verapamil, nifedipine, or nicardipine. Contractions were greatly attenuated by 3 mM LaCl3 (85.8 +/- 8.0% relaxation) and were diminished in Ca(2+)-free media (51 +/- 9% of control). The protein kinase C (PKC) inhibitor H7 (20 microM) potently and reversibly inhibited endothelin-induced contractions by 82 +/- 6% when used as post-treatment. Incubation of tissues with 20 microM H7 did not significantly affect either the strength of contractions induced with endothelin or the time required for contraction to reach plateau, but these contractions were poorly sustained compared to controls. The phospholipase C (PLC) inhibitor neomycin (10 mM) inhibited endothelin-induced contractions and it also affected the rate of force development. The phospholipase A2 (PLA2) inhibitor quinacrine had no significant effect on endothelin-induced contractions. Extracellular Ca2+ appears to enter the cell via non-potential dependent channels that can be blocked by La3+. Moreover, the potent vasoconstrictor properties of endothelin on rabbit pulmonary veins involves activation of both PLC and PKC, but not PLA2. PKC is intimately associated with maintaining the tonic phase of smooth muscle contraction.

摘要

采用组织浴技术研究了猪内皮素（内皮素1）对离体兔肺静脉环的作用。发现内皮素是这些血管的强效收缩剂，产生浓度依赖性收缩，其半数有效浓度（EC50）值为3.2±0.6×10⁻⁹ M。收缩不受钙通道拮抗剂维拉帕米、硝苯地平或尼卡地平的显著影响。3 mM的LaCl₃可使收缩显著减弱（松弛85.8±8.0%），在无钙培养基中收缩减弱（为对照的51±9%）。蛋白激酶C（PKC）抑制剂H7（20 μM）作为后处理使用时，可有效且可逆地抑制内皮素诱导的收缩，抑制率为82±6%。用20 μM H7孵育组织对内皮素诱导的收缩强度或收缩达到平台期所需的时间均无显著影响，但与对照相比，这些收缩的持续性较差。磷脂酶C（PLC）抑制剂新霉素（10 mM）抑制内皮素诱导的收缩，且还影响力的发展速率。磷脂酶A2（PLA2）抑制剂奎纳克林对内皮素诱导的收缩无显著影响。细胞外钙似乎通过可被La³⁺阻断的非电压依赖性通道进入细胞。此外，内皮素对兔肺静脉的强效血管收缩特性涉及PLC和PKC的激活，但不涉及PLA2。PKC与维持平滑肌收缩的强直期密切相关。