Goshima Y, Misu Y, Arai N, Misugi K
Department of Pharmacology, Yokohama City University School of Medicine, Japan.
Jpn J Pharmacol. 1991 Jan;55(1):93-100. doi: 10.1254/jjp.55.93.
Effects of L-DOPA (0.1-10,000 nM) on spontaneous release (Sp), evoked release (S) and tissue content (C) of dopamine (DA) were studied comparatively in superfused striatal slices from control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57 black mice to obtain evidence for L-DOPA-induced facilitation of S via presynaptic beta-adrenoceptors. In control slices, isoproterenol-induced concentration-dependent increases in S were propranolol-sensitive. L-DOPA at 0.1-3 nM tended to increase the S of DA with a concomitant tendency of increases in Sp. L-DOPA at 10-1 x 10(4) nM concentration-dependently increased Sp. L-DOPA at 1-10 microM tended to increase S and 10 microM increased C. In slices from MPTP-treated mice, the absolute amounts of Sp, S and C decreased by half compared to those in control slices. L-DOPA at 3 nM facilitated S without increasing Sp. This facilitation was antagonized by propranolol at 3 nM. L-DOPA at 30 nM decreased S from the peak facilitation, which contrasted with no effect in the control slices. However, 10-100 nM L-DOPA increased Sp more markedly than that in the control slices. L-DOPA at 100 nM increased S and C, which contrasted with no effect in the control slices. In conclusion, nanomolar L-DOPA facilitates the S of DA via presynaptic beta-adrenoceptors at concentrations lower than those required to induce conversion to DA even in striatal slices from the MPTP-treated mice model for Parkinson's disease.(ABSTRACT TRUNCATED AT 250 WORDS)
在来自对照和 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的 C57 黑小鼠的灌流纹状体切片中，比较研究了左旋多巴（0.1 - 10000 nM）对多巴胺（DA）的自发释放（Sp）、诱发释放（S）和组织含量（C）的影响，以获取左旋多巴通过突触前β-肾上腺素能受体促进诱发释放的证据。在对照切片中，异丙肾上腺素诱导的诱发释放浓度依赖性增加对普萘洛尔敏感。0.1 - 3 nM 的左旋多巴倾向于增加 DA 的诱发释放，同时自发释放也有增加趋势。10 - 1×10⁴ nM 浓度的左旋多巴使自发释放浓度依赖性增加。1 - 10 μM 的左旋多巴倾向于增加诱发释放，10 μM 时增加组织含量。在 MPTP 处理小鼠的切片中，自发释放、诱发释放和组织含量的绝对量比对照切片减少了一半。3 nM 的左旋多巴促进诱发释放而不增加自发释放。这种促进作用被 3 nM 的普萘洛尔拮抗。30 nM 的左旋多巴使诱发释放从最大促进水平下降，这与对照切片中无此效应形成对比。然而，10 - 100 nM 的左旋多巴比对照切片更显著地增加自发释放。100 nM 的左旋多巴增加诱发释放和组织含量，这与对照切片中无此效应形成对比。总之，即使在帕金森病 MPTP 处理小鼠模型的纹状体切片中，纳摩尔浓度的左旋多巴在低于诱导转化为多巴胺所需浓度时，也通过突触前β-肾上腺素能受体促进多巴胺的诱发释放。（摘要截短至 250 字）
