The effect of prostaglandin E1 (PGE1) on the spontaneous phasic contraction of the rat isolated portal vein was studied. 2. The isolated portal vein exhibited spontaneous phasic contractions. Removal of Ca2+ from Krebs-Ringer solution or application of nifedipine abolished the spontaneous contraction, indicating that the contraction depends exclusively on Ca2+ influx through L-type Ca2+ channels. On the other hand, cyclopiazonic acid (CPA), a specific inhibitor of Ca(2+)-ATPase of sarcoplasmic reticulum (SR) increased the amplitude of the contractions, suggesting that the SR regulates the spontaneous contractions negatively by sequestration of Ca2+ entering through L-type Ca2+ channels and buffering the rise in cytosolic Ca2+. 3. PGE1 increased the amplitude of the spontaneous contraction in a concentration-dependent manner without affecting the resting tension. The effect was completely abolished by nifedipine. Bay K 8644 and phenylephrine (PE) also increased the amplitude of the contraction in a concentration-dependent manner. PGE1 at a concentration of 1 microM. Bay K 8644 at 100 nM and PE at 30 nM doubled the amplitude, respectively. 4. Pretreatment with 1 microM CPA abolished the effect of PGE1, but the effects of Bay K 8644 and PE were not inhibited by pretreatment with CPA. In contrast, 10 microM ryanodine attenuated the effect of PE without affecting the contractile effect of PGE1. 5. When the SR was depleted of Ca2+ by repeated applications of caffeine in a nominally Ca(2+)-free Krebs-Ringer solution, it took about 120 s to restore the spontaneous contraction after addition of Ca2+ into the solution. In CPA-treated veins, the time taken to restore the contraction was shortened significantly. Pretreatment with 1 microM PGE1 shortened the time to the same extent as pretreatment with CPA did. 6. These results suggest that PGE1 increases the amplitude of the spontaneous phasic contraction by a different mechanism from those by which PE and Bay K 8644 increase it. Inhibition of Ca(2+)-ATPase of the SR might be involved in the vasoactive effect of PGE1.
摘要
研究了前列腺素E1（PGE1）对大鼠离体门静脉自发性节律性收缩的影响。2. 离体门静脉呈现出自发性节律性收缩。从 Krebs-Ringer 溶液中去除 Ca2+ 或应用硝苯地平可消除自发性收缩，表明该收缩完全依赖于通过 L 型 Ca2+ 通道的 Ca2+ 内流。另一方面，环匹阿尼酸（CPA），一种肌浆网（SR）Ca(2+)-ATP酶的特异性抑制剂，增加了收缩幅度，提示 SR 通过螯合经 L 型 Ca2+ 通道进入的 Ca2+ 并缓冲胞质 Ca2+ 的升高来负向调节自发性收缩。3. PGE1 以浓度依赖性方式增加自发性收缩的幅度，而不影响静息张力。该作用被硝苯地平完全消除。Bay K 8644 和去氧肾上腺素（PE）也以浓度依赖性方式增加收缩幅度。1 μM 的 PGE1、100 nM 的 Bay K 8644 和 30 nM 的 PE 分别使收缩幅度加倍。4. 用 1 μM CPA 预处理可消除 PGE1 的作用，但 Bay K 8644 和 PE 的作用不受 CPA 预处理的抑制。相反，10 μM 瑞舒伐他汀减弱了 PE 的作用，而不影响 PGE1 的收缩作用。5. 当在名义上无 Ca2+ 的 Krebs-Ringer 溶液中通过反复应用咖啡因使 SR 耗尽 Ca2+ 后，向溶液中加入 Ca2+ 后恢复自发性收缩大约需要 120 秒。在 CPA 处理的静脉中，恢复收缩所需的时间显著缩短。用 1 μM PGE1 预处理缩短时间的程度与用 CPA 预处理相同。6. 这些结果表明，PGE1 增加自发性节律性收缩幅度的机制与 PE 和 Bay K 8644 增加收缩幅度的机制不同。SR 的 Ca(2+)-ATP酶的抑制可能参与了 PGE1 的血管活性作用。
