单胺氧化酶抑制剂在大鼠脑突触体去极化诱导的5-羟色胺释放中产生非钙依赖性成分的机制。

The mechanism by which monoamine oxidase inhibitors give rise to a non-calcium-dependent component in the depolarization-induced release of 5-HT from rat brain synaptosomes.

作者信息

Evans S M, Collard K J

机构信息

Department of Physiology, University College, Cardiff.

出版信息

Br J Pharmacol. 1988 Nov;95(3):950-6. doi: 10.1111/j.1476-5381.1988.tb11725.x.

DOI:10.1111/j.1476-5381.1988.tb11725.x

PMID:3264736

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1854245/

Abstract

The effects of the monoamine oxidase inhibitors pargyline and nialamide on the Ca2+-dependency of [3H]-5-hydroxytryptamine release from superfused rat brain synaptosomes has been studied in order to evaluate the discrepancies that have occasionally been observed in studying transmitter release by in vivo and in vitro techniques. 2. The application of K+ pulses of low concentration (12.5-20 mM) caused an essentially Ca2+-dependent release of [3H]-5-HT. However, at K+ concentrations above 30 mM, a small non-Ca2+-dependent component appeared. 3. At high concentrations of K+ (30-55 mM), nialamide (18 microM) or pargyline (7 microM) increased the amount of [3H]-5-HT released which could be accounted for by an increase in the non-Ca2+-dependent component of release. 4. The elevation of the non-Ca2+-dependent component of release caused by the monoamine oxidase inhibitors was totally abolished by the inhibitors of the plasma membrane 5-HT carrier, chlomipramine (500 nM), citalopram (50 nM) and fluoxetine (1 microM). 5. The results suggest that the non-Ca2+-dependent component of release seen with high depolarizing concentrations of K+, particularly in the presence of monoamine oxidase inhibitors, is caused by the efflux of [3H]-5-HT through the plasma membrane carrier which seems to be activated during depolarization. 6. The significance of these findings to the physiological in vivo situation, and to the use of in vitro preparations in the study of transmitter release is discussed.

摘要

为了评估在通过体内和体外技术研究递质释放时偶尔观察到的差异，研究了单胺氧化酶抑制剂优降宁和尼亚酰胺对超融合大鼠脑突触体中[3H]-5-羟色胺释放的钙依赖性的影响。2. 低浓度（12.5 - 20 mM）的钾脉冲应用导致[3H]-5-羟色胺的释放基本上依赖于钙。然而，当钾浓度高于30 mM时，出现了一个小的非钙依赖性成分。3. 在高浓度钾（30 - 55 mM）时，尼亚酰胺（18 microM）或优降宁（7 microM）增加了[3H]-5-羟色胺的释放量，这可以通过释放的非钙依赖性成分的增加来解释。4. 单胺氧化酶抑制剂引起的释放的非钙依赖性成分的升高被质膜5-羟色胺载体抑制剂氯米帕明（500 nM）、西酞普兰（50 nM）和氟西汀（1 microM）完全消除。5. 结果表明，在高去极化浓度的钾存在下，特别是在单胺氧化酶抑制剂存在的情况下，观察到的释放的非钙依赖性成分是由[3H]-5-羟色胺通过质膜载体的流出引起的，这种载体似乎在去极化过程中被激活。6. 讨论了这些发现对体内生理情况以及在递质释放研究中使用体外制剂的意义。