Ronken E, Mulder A H, Schoffelmeer A N
Department of Pharmacology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
J Neurochem. 1993 Nov;61(5):1634-9. doi: 10.1111/j.1471-4159.1993.tb09797.x.
The presynaptic regulation of stimulated dopamine release from superfused rat striatal synaptosomes by opioids and gamma-aminobutyric acid (GABA) was studied. It was found that in addition to dopamine D2 autoreceptors, calcium-dependent K(+)-stimulated [3H]dopamine release was inhibited through activation of a homogeneous population of kappa-opioid receptors in view of the potent inhibitory effect of the kappa-selective agonist U69,593 (EC50 0.2 nM) and its antagonism by norbinaltorphimine. Neither mu- nor delta-selective receptor agonists affected release of [3H]-dopamine. In addition, GABA potently inhibited the evoked [3H]dopamine release (EC50 0.4 nM) through activation of GABAA receptors in view of the GABA-mimicking effect of muscimol, the sensitivity of its inhibitory effect to picrotoxin and bicuculline, and the absence of an effect of the GABAB receptor agonist baclofen. In the presence of a maximally effective concentration of GABA, U69,593 did not induce an additional release-inhibitory effect, indicating that these receptors and the presynaptic D2 receptor are colocalized on the striatal dopaminergic nerve terminals. The excitatory amino acid agonists N-methyl-D-aspartate and kainate, as well as the cholinergic agonist carbachol, stimulated [3H]dopamine release, which was subject to kappa-opioid receptor-mediated inhibition. In conclusion, striatal dopamine release is under regulatory control of multiple excitatory and inhibitory neurotransmitter by activation of colocalized presynaptic receptors for excitatory amino acids, acetylcholine, dopamine, dynorphins, and GABA within the dopaminergic nerve terminals. Together, these receptors locally control ongoing dopamine neurotransmission.
研究了阿片类药物和γ-氨基丁酸（GABA）对灌流大鼠纹状体突触体中刺激多巴胺释放的突触前调节。结果发现，除多巴胺D2自身受体外，鉴于κ-选择性激动剂U69,593（EC50 0.2 nM）的强效抑制作用及其被纳洛酮拮抗，钙依赖性K(+)刺激的[3H]多巴胺释放通过激活同质的κ-阿片受体而受到抑制。μ-和δ-选择性受体激动剂均不影响[3H]多巴胺的释放。此外，鉴于蝇蕈醇的GABA模拟作用、其抑制作用对印防己毒素和荷包牡丹碱的敏感性以及GABAB受体激动剂巴氯芬无作用，GABA通过激活GABAA受体有效抑制诱发的[3H]多巴胺释放（EC50 0.4 nM）。在最大有效浓度的GABA存在下，U69,593未诱导额外的释放抑制作用，表明这些受体与突触前D2受体共定位于纹状体多巴胺能神经末梢。兴奋性氨基酸激动剂N-甲基-D-天冬氨酸和 kainate以及胆碱能激动剂卡巴胆碱刺激[3H]多巴胺释放，其受到κ-阿片受体介导的抑制。总之，纹状体多巴胺释放受多种兴奋性和抑制性神经递质的调节控制，通过激活多巴胺能神经末梢内兴奋性氨基酸、乙酰胆碱、多巴胺、强啡肽和GABA的共定位突触前受体。这些受体共同局部控制正在进行的多巴胺神经传递。
