MODULATION OF GAMMA-AMINOBUTYRIC-ACID RELEASE IN CEREBRAL-CORTEX BY FLUORIDE, PHORBOL ESTER, AND PHOSPHODIESTERASE INHIBITORS - DIFFERENTIAL SENSITIVITY OF ACETYLCHOLINE-RELEASE TO FLUORIDE AND K+ CHANNEL BLOCKERS

被引:20
作者
GARDINER, IM [1 ]
DEBELLEROCHE, J [1 ]
机构
[1] CHARING CROSS & WESTMINSTER MED SCH,DEPT BIOCHEM,FULHAM PALACE RD,LONDON W6 8RF,ENGLAND
关键词
Cerebral cortex; Fluoride; G protein activation; GABA release; Phorbol diacetate; Tetrahydroaminoacridine;
D O I
10.1111/j.1471-4159.1990.tb01939.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In this study we have used fluoride as a tool to investigate the involvement of G protein‐coupled effector systems in the regulation of the depolarization‐induced release of γ‐aminobutyric acid (GABA) from rat cerebral cortex. To distinguish among the activating effects of NaF on G proteins linked to different effectors, such as adenylate cyclase, polyphosphoinositide phospholipase C, and K+ channels, agents specific to these effectors have been used in parallel. NaF induced a marked dose‐dependent facilitation of the K+‐evoked release of [14C]GABA, with an EC50 of 1.26 mM, increasing release by 103% at 5 mM NaF. No effect on basal release was seen up to 3 mM NaF, and no modulation of [3H]acetylcholine (ACh) release was seen up to 5 mM NaF. Phorbol 12,13‐diacetate (PDA) produced a similar dose‐dependent facilitation of the K+‐evoked release of [14C]GABA, potentiating the release of [14C]GABA by 50% at 10 μM PDA. The phosphodiesterase inhibitors, 3‐isobutyl‐1‐methylxanthine (IBMX) and theophylline, inhibited the K+‐evoked release of [14C]GABA, and IBMX reversed the NaF facilitation of GABA release in a dose‐dependent manner (pA2 2.57). The K+ channel blocker (IA current) tetrahydroaminoacridine (THA), which markedly inhibits the K+‐evoked release of [14C]GABA, also reversed the NaF facilitatory effect, but the release of [3H]ACh was less sensitive to the inhibitory effect of THA. On the other hand, the K+ channel blocker, tetraethylammonium, which has no effect on the release of [14C]GABA, caused a significant facilitation of K+‐evoked release of [3H]ACh. From these studies, it is concluded that GABA release in cerebral cortex is subject to regulation by G protein‐linked effector systems that are distinct from those affecting the release of [3H]ACh in cerebral cortex. Copyright © 1990, Wiley Blackwell. All rights reserved
引用
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页码:1130 / 1135
页数:6
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