The Effects of Dopamine D-1 and D-2 Receptor Subtype Agonists on Nigrostriatal Opioid Dynorphin and Enkephalin Immunostaining in 6-Hydroxydopamine Lesioned Rats

多巴胺D-1及D-2受體亞型致效劑對經6-羥基多巴胺破壞多巴胺神經元之大白鼠內黑質—紋狀體徑路中類鴉片勝肽免疫組織染色之影響

江漢光(Hann-Kuang Jiang) ； 王家儀(Jia-Yi Wang)

《The Chinese Journal of Physiology》 34卷4期 (1991/12) Pp. 413-425

摘要

我們先前利用放射免疫分析定量之方法已經證明黑質－紋狀體多巴胺徑路對調節紋狀體類嗎啡胜肽dynorphin及enkephalin扮有重要角色，並且多巴胺系統抑制enkephalin神經系統，但是刺激dynorphin神經系統。本實驗之目的是進一步用免疫組織染色之方法來確定此結果，並研究何種多巴胺受體亞型來媒介此多巴胺之調節作用。我們準備三組大白鼠，將神經毒素6-羥基多巴胺(10μg/0.5μl)注射入單側黑質，對側黑質則僅注射人工腦脊髓液作為對照。二週後分別給予三組大白鼠多巴胺D-1受體致效劑SKF-38393(5mg/kg)，D-2受體致效劑LY-171555(1mg/kg)，及鹽水，連續7天腹腔注射於二週前單側黑質已遭6-羥基多巴胺破壞之大白鼠。三組大白鼠於最後一次注射之16小時後，以固定液灌流，取出腦組織，並切片(50μm)作dynorphin A(1-17)及[Met^5]-enkephalin之免疫組織染色。我們的結果顯示黑質6-羥基多巴胺破壞後導致紋狀體及黑質之dynorphin A(1-17)之染色比對側減少。但是，SKF-38393則導致與上述相反結果，且使dynorphin A(1-17)之染色在6-OHDA破壞之同側染色更深。LY-171555則無此效果。相反地，enkephalin之免疫組織染色程度則因6-OHDA之破壞而增加，且此效果可被SKF-38393阻斷，但LY-171555則無此作用。這些結果與我們先前利用放射免疫分析定量之結果一致，且支持多巴胺D-1受體媒介對dynorphin系統興奮作用，然而卻抑制enkephalin系統之理論。並且可進一步推論多巴胺D-1亞型受體及這些類嗎啡胜肽可能與精神及神經疾病之病理及藥物治療之機轉有關。

並列摘要

Jiang, H.-K., and J.-Y. Wang. The effects of dopamine D-1 and D-2 receptor subtype agonists on nigrostriatal opioid dynorphin and enkephalin immunostaining in 6-hydroxy- dopamine lesioned rats. Chinese J. Physiol. 34(4):413-425, 1991. Using selective neurotoxin lesioning and immunocytochemical techniques, the effects of dopamine receptor subtypes stimulation by selective subtype agonists in the modulation of striatal opioid dynorphin and enkephalin were characterized in the rat basal ganglia. Tissue staining with specific antibodies against either dynorphin A (1-17) or [Met^5]-enkephalin was examined in the striatum and substantia nigra following unilateral nigrostriatal dopaminergic lesioning by the neurotoxin 6-hydroxydopamine (6-OHDA). Two weeks later three groups of five 6-OHDA lesioned rats were repeatedly treated with either the dopamine D-1 receptor agonist SKF-38393 (5mg.kg, i.p.), D-2 receptor agonist LY-171555 (1mg/kg, i.p.) or saline for 7 days and similar immunostaining procedures were employed. The results indicated that 6-OHDA lesioning alone led to reduction in dynorphin A (1-17) immunostaining in substantia nigra and striatum when compared to the sham-lesioned contralateral side. However, SKF-3 8393 treatment reversed that pattern and caused more intense dynorphin A (1-17) immunostaining than the lesion side, while LY-17 1555 had no effect. In contrast, enkephalin immunostaining was increased by 6-OHDA lesioning, and the effect was abolished by SKF-38393 but not LY-17 1555. These results are in agreement with previously replorted radioimmunoassay findings and are compatible with the proposal that dopamine D-1 receptors mediate the excitatory effect on the dynorphinergic system while inhibiting the enkephalinergic system.

並列關鍵字

nigrostriatum ； opioid peptides ； dopamine receptor subtypes ； immunostaining