罂粟碱对兔血管平滑肌细胞中去甲肾上腺素诱导的膜电流的调节作用。

Modulation of noradrenaline-induced membrane currents by papaverine in rabbit vascular smooth muscle cells.

作者信息

Wang Q, Large W A

机构信息

Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, London.

出版信息

J Physiol. 1991 Aug;439:501-12. doi: 10.1113/jphysiol.1991.sp018678.

DOI:10.1113/jphysiol.1991.sp018678

PMID:1716677

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1180120/

Abstract

The modulation of noradrenaline-induced membrane currents by papaverine was studied with the nystatin whole-cell technique in freshly isolated rabbit ear artery and portal vein cells. 2. At a holding potential of -50 mV (in potassium-free conditions), papaverine inhibited the Ca(2+)-activated inward chloride current ICl(Ca) evoked by ionophoretic application of noradrenaline in rabbit portal vein cells in a concentration-dependent (10(-5)-10(-4) M) manner. 3. With potassium-containing solutions (at 0 mV) 10(-4) M-papaverine reversibly abolished the Ca(2+)-activated outward potassium current IK(Ca) induced by noradrenaline in both protal vein and ear artery cells. Occasionally, 10(-4) M-papaverine itself activated IK(Ca) before it abolished the response to noradrenaline. 4. Higher concentrations of papaverine (up to 10(-3) M) always evoked both ICl(Ca) and IK(Ca) at -50 and 0 mV respectively, before it abolished these responses to noradrenaline in both ear artery and portal vein cells. In the presence of 10(-3) M-papaverine higher doses of noradrenaline evoked the non-selective cation current in some portal vein cells. 5. In the presence of 10(-2) M-caffeine, which elicited both IK(Ca) and ICl(Ca), papaverine (10(-3) M) failed to activate either current and 10(-3) M-papaverine reduced the caffeine-induced IK(Ca) by 94%. In contrast, IK(Ca) induced by the calcium ionophore ionomycin was unaffected by papaverine. In Ca(2+)-free, 1 mM-EGTA external solutions, 10(-3) M-papaverine still induced IK(Ca) and blocked the response to noradrenaline. 6. The alpha 1-adrenoceptor antagonist prazosin (5 x 10(-8) M) completely blocked the noradrenaline-induced IK(Ca) but currents evoked by papaverine (10(-3) M) were unaffected by prazosin. 7. It was concluded that papaverine modulated noradrenaline-induced membrane currents in vascular smooth muscle cells by releasing and depleting caffeine-sensitive intracellular Ca2+ stores.

摘要

采用制霉菌素全细胞技术，在新鲜分离的兔耳动脉和门静脉细胞中研究了罂粟碱对去甲肾上腺素诱导的膜电流的调节作用。2. 在 -50 mV 的钳制电位下（在无钾条件下），罂粟碱以浓度依赖性（10⁻⁵ - 10⁻⁴ M）方式抑制了离子电泳施加去甲肾上腺素在兔门静脉细胞中诱发的 Ca²⁺ 激活内向氯电流 ICl(Ca)。3. 在含钾溶液中（在 0 mV 时），10⁻⁴ M 的罂粟碱可逆地消除了去甲肾上腺素在门静脉和耳动脉细胞中诱导的 Ca²⁺ 激活外向钾电流 IK(Ca)。偶尔，10⁻⁴ M 的罂粟碱在消除对去甲肾上腺素的反应之前自身会激活 IK(Ca)。4. 更高浓度的罂粟碱（高达 10⁻³ M）在 -50 和 0 mV 时分别总是先诱发 ICl(Ca) 和 IK(Ca)，然后才消除耳动脉和门静脉细胞中对去甲肾上腺素的这些反应。在存在 10⁻³ M 罂粟碱的情况下，更高剂量的去甲肾上腺素在一些门静脉细胞中诱发了非选择性阳离子电流。5. 在存在 10⁻² M 咖啡因（其诱发了 IK(Ca) 和 ICl(Ca)）的情况下，罂粟碱（10⁻³ M）未能激活任何一种电流，且 10⁻³ M 的罂粟碱使咖啡因诱导的 IK(Ca) 降低了 94%。相比之下，钙离子载体离子霉素诱导的 IK(Ca) 不受罂粟碱影响。在无 Ca²⁺、1 mM - EGTA 的外部溶液中，10⁻³ M 的罂粟碱仍能诱导 IK(Ca) 并阻断对去甲肾上腺素的反应。6. α1 - 肾上腺素能受体拮抗剂哌唑嗪（5×10⁻⁸ M）完全阻断了去甲肾上腺素诱导的 IK(Ca)，但罂粟碱（10⁻³ M）诱发的电流不受哌唑嗪影响。7. 得出的结论是，罂粟碱通过释放和耗尽对咖啡因敏感的细胞内 Ca²⁺ 储存来调节血管平滑肌细胞中去甲肾上腺素诱导的膜电流。