RELATIONSHIP BETWEEN CYTOSOLIC CALCIUM-CONCENTRATION AND FORCE IN THE PAPAVERINE-INDUCED RELAXATION OF MEDIAL STRIPS OF PIG CORONARY-ARTERY
RELATIONSHIP BETWEEN CYTOSOLIC CALCIUM-CONCENTRATION AND FORCE IN THE PAPAVERINE-INDUCED RELAXATION OF MEDIAL STRIPS OF PIG CORONARY-ARTERY
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DOI：
10.1111/j.1476-5381.1994.tb14763.x
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发表时间：
1994-02-01
影响因子：
7.3
通讯作者：
KANAIDE, H
中科院分区：
文献类型：
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作者：
AOKI, H;NISHIMURA, J;KANAIDE, H
1 使用前表面荧光测定法和负载 fura-2 的猪冠状动脉内侧条带研究了罂粟碱诱导的血管舒张机制。 2 在细胞外Ca2+(1.25x10(-3)M)存在下，组胺(10(-4)M)引起胞浆钙浓度突然升高，[Ca2+](i)在12s内达到峰值(第一阶段)；轻微肩变后，[Ca2+](i)逐渐下降，达到持续水平（第二阶段）。力量迅速上升，在3分钟内达到最高水平，然后逐渐下降。罂粟碱 (10(-7)-10(-5)M) 以浓度依赖性方式抑制 [Ca2+](i) 升高的第一阶段和第二阶段以及组胺诱导的力的发展。 3 在细胞外 Ca2+ 缺失的情况下，组胺 (10(-4)M ) 会诱导 [Ca2+](i) 和力短暂增加，而罂粟碱 (10(-7)-10(-5)M) 会以浓度依赖性方式抑制这两者。当罂粟碱被洗掉后，第二次使用 10(-4)M 组胺也会诱导 [Ca2+](i) 和力的短暂增加。第一个响应越小，第二个响应越大。在罂粟碱存在的情况下，第一次和第二次施用组胺从细胞内储存释放的[Ca2+](i)总量比不存在罂粟碱时要小，从而表明组胺敏感储存中的Ca2+减少。然而，虽然罂粟碱(10(-5)M)不影响2x10(-2)M咖啡因诱导的[Ca2+](i)短暂增加，但收缩受到抑制。 4 对于给定水平的 [Ca2+](i)，在高 K+ 去极化期间，累积应用组胺 (10(-7)M-10(-4)M) 产生的力大于累积应用细胞外 Ca2+ (0-7.5x10(-3)M) 观察到的力。罂粟碱 (10(-7)M-10(-5)M) 以浓度依赖性方式抑制 [Ca2+](i) 的增加以及高 K+ 去极化期间组胺和细胞外 Ca2+ 累积应用引起的力。通过用 K+ 去极化获得的 [Ca2+](i) 力曲线，但不是在应用组胺期间获得的，通过罂粟碱向右移动。地尔硫卓（10(-7)M）是一种与 10(-5)M 罂粟碱具有相似松弛程度的浓度，不会改变高 K+ 条件下获得的 [Ca2+](i) 力曲线。硝酸甘油(10(-6)M)和异丙肾上腺素(10(-6)M)使[Ca2+](i)-力曲线向右移动的程度比10(-5)M罂粟碱更大。 5 这些发现表明罂粟碱通过两种机制放松猪冠状动脉的内侧带。第一个主要是由于 [Ca2+](i) 的减少，不仅通过电压依赖性或受体操作的 Ca2+ 通道抑制 Ca2+ 流入，而且还通过抑制激动剂诱导的细胞内 Ca2+ 释放。这可能是由于组胺信号转导途径受到干扰以及组胺敏感储备中 Ca2+ 的消耗而发生的。其次，某些收缩机制的[Ca2+](i)敏感性可能会最小化降低。
1 The mechanisms of vasorelaxation induced by papaverine were investigated using front-surface fluorometry and fura-2-loaded medial strips of the pig coronary artery. 2 In the presence of extracellular Ca2+ (1.25x10(-3)M), histamine (10(-4)M) induced abrupt elevations of cytosolic calcium concentration, [Ca2+](i) reaching a peak within 12s (the first phase); after making a slight shoulder, [Ca2+](i) declined gradually to reach sustained levels (the second phase). Force rapidly rose to reach maximum levels in 3 min, then gradually declined. Papaverine (10(-7)-10(-5)M) inhibited both the first and the second phases of [Ca2+](i) elevation and the development of force induced by histamine, in a concentration-dependent manner. 3 In the absence of extracellular Ca2+, histamine (10(-4)M ) induced a transient increase in [Ca2+](i) and force, both of which were inhibited in a concentration-dependent manner by papaverine (10(-7)-10(-5)M). When papaverine was washed out, a second application of 10(-4)M histamine also induced transient increases in [Ca2+](i) and force. The smaller the first response, the greater was the second response. The total amount of [Ca2+](i) released from intracellular stores by the first and second application of histamine in the presence of papaverine was smaller than in its absence, thereby indicating a reduction of Ca2+ in the histamine-sensitive store. However, while papaverine (10(-5)M) did not affect the transient increase in [Ca2+](i) induced by 2x10(-2)M caffeine, contractions were inhibited. 4 For a given level of [Ca2+](i), the force developed with the cumulative application of histamine (10(-7)M-10(-4)M) was greater than that observed with the cumulative application of extracellular Ca2+ (0-7.5x10(-3)M) during high K+ depolarization. Papaverine (10(-7)M-10(-5)M) suppressed, in a concentration-dependent manner, the increase in [Ca2+](i) and the force induced by cumulative applications of both histamine and extracellular Ca2+ during high K+ depolarization. The [Ca2+](i)-force curve obtained by depolarization with K+, but not that obtained during histamine application, was shifted to the right by papaverine. Diltiazem, 10(-7)M, a concentration causing a similar degree of relaxation to 10(-5)M papaverine, did not shift the [Ca2+](i)-force curve obtained with high K+. Nitroglycerin (10(-6)M) and isoprenaline (10(-6)M) shifted the [Ca2+](i)-force curve to the right to a greater extent than did 10(-5)M papaverine. 5 These findings suggest that papaverine relaxes medial strips of the porcine coronary artery by two mechanisms. The first is mainly due to a decrease in [Ca2+](i), not only through inhibiting Ca2+ influx through either voltage-dependent or receptor-operated Ca2+ channels, but also by inhibiting agonist-induced intracellular Ca2+ release. This occurs presumably by interference with the signal transduction pathway for histamine and by a depletion of Ca2+ in histamine-sensitive stores. Secondly, the [Ca2+](i)-sensitivity of certain contractile mechanisms may be minimally decreased.