Pittaluga A, Asaro D, Pellegrini G, Raiteri M
Istituto di Farmacologia e Farmacognosia, Università di Genova, Italy.
Eur J Pharmacol. 1987 Nov 24;144(1):45-52. doi: 10.1016/0014-2999(87)90007-0.
The presence of autoreceptors for gamma-aminobutyric acid (GABA) in the CNS was reinvestigated using rat cortex synaptosomes prelabeled with [3H]GABA and exposed to GABA by superfusion in the presence of a new GABA uptake inhibitor, N-(4,4-diphenyl-3-butenyl)-nipecotic acid (SK&F 89976A). This compound itself did not increase the basal or the depolarization-evoked release of [3H]GABA. GABA reduced in a concentration-dependent way the release of [3H]GABA evoked by 15 mM K+. The effect was not antagonized by bicuculline, picrotoxin or by the new GABAA antagonist SR 95531. The GABAA agonist muscimol did not affect [3H]GABA release. This was reduced by (-)baclofen (but not by the (+) isomer) and the concentration-inhibition curve of (-)baclofen was superimposable on to that of GABA. Also the K+-evoked release of endogenous GABA was stereoselectively and concentration dependently inhibited by the (-) enantiomer of baclofen. It is concluded that the release of GABA from rat cortical nerve endings may be inhibited through the activation of autoreceptors which appear to belong to the GABAB type.
利用预先用[³H]γ-氨基丁酸（GABA）标记的大鼠皮层突触体，并在一种新的GABA摄取抑制剂N-(4,4-二苯基-3-丁烯基)-哌啶甲酸（SK&F 89976A）存在的情况下通过灌流使其暴露于GABA，对中枢神经系统中GABA自身受体的存在情况进行了重新研究。该化合物本身并不会增加[³H]GABA的基础释放或去极化诱发释放。GABA以浓度依赖性方式降低了由15 mM钾离子诱发的[³H]GABA释放。荷包牡丹碱、印防己毒素或新的GABAA拮抗剂SR 95531均未拮抗该效应。GABAA激动剂蝇蕈醇不影响[³H]GABA释放。(-)巴氯芬（而非(+)异构体）可降低该释放，且(-)巴氯芬的浓度-抑制曲线与GABA的曲线重叠。此外，巴氯芬的(-)对映体对内源性GABA的钾离子诱发释放具有立体选择性且浓度依赖性抑制作用。得出的结论是，大鼠皮层神经末梢释放GABA可能通过激活似乎属于GABAB型的自身受体而受到抑制。
