兔肺动脉中[3H]去甲肾上腺素释放对细胞内钠的依赖性

Dependence of release of [3H]noradrenaline from rabbit pulmonary artery on internal sodium.

作者信息

Török T L, Tóth P T, Tóthfalusi L, Azzidani A M, Magyar K

机构信息

Department of Pharmacodynamics, Semmelweis University of Medicine, Budapest, Hungary.

出版信息

J Physiol. 1992 Dec;458:11-25. doi: 10.1113/jphysiol.1992.sp019403.

DOI:10.1113/jphysiol.1992.sp019403

PMID:1338787

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1175141/

Abstract

[3H]Noradrenaline ([3H]NA) release from the isolated main pulmonary artery of the rabbit has been measured in the presence of uptake blockers (cocaine, 3 x 10(-5) M, and corticosterone, 5 x 10(-5) M) and after blocking the monoamine oxidase enzyme by pargyline (1.2 x 10(-4) M). 2. In normal Krebs solution Mn2+ (2 mM) significantly inhibited both [3H]NA release (approximately 80%; P < 0.001) and the contraction following 2 Hz field stimulation. 3. In Ca(2+)-free, EGTA (1 mM)-containing solution, the Na+ pump was inhibited by removal of K+ from the external medium. In Na+ pump-inhibited arteries, 2 mM Mn2+ (free Mn2+, 1 mM) increased the spontaneous release of [3H]NA according to the time of Na+ loading. TTX (10(-7) M) did not inhibit significantly the Mn(2+)-induced [3H]NA release from Na(+)-loaded preparations (percentage inhibition, approximately 24; P > 0.30). 4. Without Na+ loading (Ca2+ free, EGTA alone), Mn2+ failed to promote 3H release from arteries. 5. With constant Na+ loading (120 min 'K(+)-free' perfusion in Ca(2+)-free, 1 mM EGTA-containing solution), the release of 3H was also directly dependent on free Mn2+ concentration (0.2, 0.6 and 1 mM). 6. The Mn2+ (2 mM; free Mn2+, 1 mM)-induced 3H release from Na(+)-loaded nerves (120 min 'K(+)-free', perfusion) was further enhanced, when external Na+ was simultaneously reduced from 139.2 to 26.2 mM (choline+ or sucrose substitution). 7. Diphenylhydantoin (DPH, 10(-4) M) significantly reduced the Mn(2+)-evoked 3H release (approximately 44%; P < 0.02) when it was present during 'K(+)-free', perfusion. 8. Mn2+ was ineffective in releasing 3H if the Na+ pump was previously reactivated by readmission of K+ to Na(+)-loaded arteries. 9. It is concluded that in Ca(2+)-free solution Mn2+ releases neurotransmitter in a manner which depends on the degree of loading with internal Na+. The results suggest this depends at least partly on a block of Ca2+ efflux.

摘要

在摄取阻滞剂（可卡因，3×10⁻⁵ M，和皮质酮，5×10⁻⁵ M）存在的情况下，以及在用帕吉林（1.2×10⁻⁴ M）阻断单胺氧化酶后，测量了兔离体主肺动脉中[³H]去甲肾上腺素（[³H]NA）的释放。2. 在正常的 Krebs 溶液中，Mn²⁺（2 mM）显著抑制[³H]NA 的释放（约 80%；P < 0.001）以及 2 Hz 场刺激后的收缩。3. 在无钙、含 EGTA（1 mM）的溶液中，通过从外部介质中去除 K⁺来抑制 Na⁺泵。在 Na⁺泵受抑制的动脉中，2 mM Mn²⁺（游离 Mn²⁺，1 mM）根据 Na⁺负载时间增加[³H]NA 的自发释放。TTX（10⁻⁷ M）并未显著抑制 Mn²⁺诱导的来自 Na⁺负载制剂的[³H]NA 释放（抑制百分比，约 24；P > 0.30）。4. 在无 Na⁺负载（无钙，仅含 EGTA）的情况下，Mn²⁺未能促进动脉中³H 的释放。5. 在持续 Na⁺负载（在无钙、含 1 mM EGTA 的溶液中进行 120 分钟“无 K⁺”灌注）时，³H 的释放也直接依赖于游离 Mn²⁺浓度（0.2、0.6 和 1 mM）。6. 当外部 Na⁺同时从 139.2 mM 降至 26.2 mM（用胆碱⁺或蔗糖替代）时，Mn²⁺（2 mM；游离 Mn²⁺，1 mM）诱导的来自 Na⁺负载神经（120 分钟“无 K⁺”灌注）的³H 释放进一步增强。7. 当在“无 K⁺”灌注期间存在二苯乙内酰脲（DPH，10⁻⁴ M）时，它显著降低了 Mn²⁺诱发的³H 释放（约 44%；P < 0.02）。8. 如果通过将 K⁺重新引入 Na⁺负载的动脉中预先重新激活 Na⁺泵，Mn²⁺在释放³H 方面无效。9. 得出的结论是，在无钙溶液中，Mn²⁺以依赖于内部 Na⁺负载程度的方式释放神经递质。结果表明，这至少部分取决于 Ca²⁺外流的阻断。