l-DOPA 受体 GPR143 通过 PC12 细胞中的 L 型钙通道抑制神经元生长

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY Journal of pharmacological sciences Pub Date : 2024-07-06 DOI:10.1016/j.jphs.2024.07.003

Miyu Inoue, Daiki Masukawa, Yoshio Goshima

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引用次数: 0

摘要

眼白化病 1（OA1）/G 蛋白偶联受体（GPR）143 的基因产物是治疗帕金森病最有效的药物 L-3,4-二羟基苯丙氨酸（l-DOPA）的受体。当过量表达时，人类野生型 GPR143（而非其突变体）会抑制 PC12 细胞中神经元的生长。我们研究了 GPR143 抑制神经元生长的下游信号通路。硝苯地平使 GPR143 诱导的神经元外生抑制恢复到对照转染的水平，但不影响 GPR143 敲除细胞的外生。西尼地平和氟桂利嗪也抑制了 GPR143 诱导的抑制作用，但即使在 GPR143 敲除的细胞中，它们在较高浓度下仍有作用。这些结果表明，GPR143 通过 L 型钙通道调节神经元的生长。

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l-DOPA receptor GPR143 inhibits neurite outgrowth via L-type calcium channels in PC12 cells

The gene product of ocular albinism 1 (OA1)/G-protein-coupled receptor (GPR)143 is a receptor for L-3,4-dihydroxyphenylanine (l-DOPA), the most effective agent for Parkinson's disease. When overexpressed, human wild-type GPR143, but not its mutants, inhibits neurite outgrowth in PC12 cells. We investigated the downstream signaling pathway for GPR143-induced inhibition of neurite outgrowth. Nifedipine restored GPR143-induced neurite outgrowth inhibition to the level of control transfectant but did not affect outgrowth in GPR143-knockdown cells. Cilnidipine and flunarizine also suppressed the GPR143-induced inhibition, but their effects at higher concentrations still occurred even in GPR143-knockdown cells. These results suggest that GPR143 regulates neurite outgrowth via L-type calcium channel(s).

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来源期刊

Journal of pharmacological sciences 医学-药学

CiteScore

6.20

自引率

2.90%

发文量

104

审稿时长

31 days

期刊介绍： Journal of Pharmacological Sciences (JPS) is an international open access journal intended for the advancement of pharmacological sciences in the world. The Journal welcomes submissions in all fields of experimental and clinical pharmacology, including neuroscience, and biochemical, cellular, and molecular pharmacology for publication as Reviews, Full Papers or Short Communications. Short Communications are short research article intended to provide novel and exciting pharmacological findings. Manuscripts concerning descriptive case reports, pharmacokinetic and pharmacodynamic studies without pharmacological mechanism and dose-response determinations are not acceptable and will be rejected without peer review. The ethnopharmacological studies are also out of the scope of this journal. Furthermore, JPS does not publish work on the actions of biological extracts unknown chemical composition.