Ronken E, Van Muiswinkel F L, Mulder A H, Schoffelmeer A N
Department of Pharmacology, Free University, Medical Faculty, Amsterdam, Netherlands.
Eur J Pharmacol. 1993 Jan 19;230(3):349-55. doi: 10.1016/0014-2999(93)90572-y.
The effects of selective opioid agonists on the evoked release of [3H]dopamine and [3H]noradrenaline were studied in cultured dopaminergic neurons of the ventral mesencephalon (containing the substantia nigra and ventral tegmental area) and in cultured neurons of the noradrenergic locus coeruleus, respectively. The cultures were prepared from embryonic day 15 rat brains. After 9 days in culture, the calcium-dependent release of [3H]dopamine from dopaminergic substantia nigra/ventral tegmental area neurons induced by 23 mM k+ appeared to be inhibited exclusively by activation of kappa-opioid receptors, as [3H]dopamine release was inhibited selectively by the kappa agonists U69,593 and dynorphin-(1-13) (EC50 8 and 5 nM, respectively), and this inhibitory effect was antagonized by the kappa-selective antagonist nor-binaltorphimine (Ki 0.07 nM). In contrast, cultured noradrenergic locus coeruleus neurons appeared to contain release-inhibitory mu-opioid receptors only, as evoked [3H]noradrenaline release was inhibited selectively by the mu agonist [D-Ala2, MePhe4, Gly-ol5]enkephalin (EC50 45 nM), a response that was antagonized by the preferential mu antagonist naloxone (Ki = 0.7 nM). The delta-opioid receptor agonist [D-Ser2(O-butyl), Leu5]enkephalyl-Thr6 did not affect catecholamine release. Dopamine release from cultured ventral mesencephalic neurons, induced by 100 microM N-Methyl-D-Aspartate (NMDA), also appeared to be subject to kappa receptor-mediated inhibition, whereas NMDA-induced noradrenaline release from cultured locus coeruleus neurons was under the inhibitor control of mu receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
分别在中脑腹侧（包含黑质和腹侧被盖区）的培养多巴胺能神经元以及去甲肾上腺素能蓝斑核的培养神经元中，研究了选择性阿片样物质激动剂对[3H]多巴胺和[3H]去甲肾上腺素诱发释放的影响。培养物取自胚胎第15天的大鼠脑。培养9天后，23 mM钾离子诱导的多巴胺能黑质/腹侧被盖区神经元中[3H]多巴胺的钙依赖性释放似乎仅受κ-阿片样物质受体激活的抑制，因为[3H]多巴胺释放被κ激动剂U69,593和强啡肽-(1-13)（EC50分别为8和5 nM）选择性抑制，且这种抑制作用被κ选择性拮抗剂去甲双丙戊啡（Ki 0.07 nM）拮抗。相反，培养的去甲肾上腺素能蓝斑核神经元似乎仅含有释放抑制性μ-阿片样物质受体，因为诱发的[3H]去甲肾上腺素释放被μ激动剂[D-丙氨酸2，甲硫苯丙氨酸4，甘醇5]脑啡肽（EC50 45 nM）选择性抑制，该反应被优先的μ拮抗剂纳洛酮（Ki = 0.7 nM）拮抗。δ-阿片样物质受体激动剂[D-丝氨酸2（O-丁基），亮氨酸5]脑啡肽-苏氨酸6不影响儿茶酚胺释放。100 microM N-甲基-D-天冬氨酸（NMDA）诱导的培养中脑腹侧神经元多巴胺释放似乎也受κ受体介导的抑制，而NMDA诱导的培养蓝斑核神经元去甲肾上腺素释放受μ受体的抑制性控制。（摘要截短于250字）
