Departamento de Fisiología, Biofísica y Neurociencias. Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico.
Departamento de Farmacología. Facultad de Medicina Veterinaria, Universidad Autónoma del Estado de México, Mexico City, Mexico.
Synapse. 2022 Sep;76(11-12):e22246. doi: 10.1002/syn.22246. Epub 2022 Jul 23.
Striatal medium-sized spiny neurons express mRNA and protein of GPR55 receptors that stimulate neurotransmitter release; thus, GPR55 could be sent to nigral striatal projections, where it might modulate GABA release and motor behavior. Here, we study the presence of GPR55 receptors at striato-nigral terminals, their modulation of GABA release, their signaling pathway, and their effect on motor activity. By double immunohistochemistry, we found the colocation of GPR55 protein and substance P in the dorsal striatum. In slices of the rat substantia nigra, the GPR55 agonists LPI and O-1602 stimulated [ H]-GABA release induced by high K depolarization in a dose-dependent manner. The antagonists CID16020046 and cannabidiol prevented agonist stimulation in a dose-dependent way. The effect of GPR55 on nigral [ H]-GABA release was prevented by lesion of the striatum with kainic acid, which was accompanied by a decrement of GPR55 protein in nigral synaptosomes, indicating the presynaptic location of receptors. The depletion of internal Ca stores with thapsigargin did not prevent the effect of LPI on [ H]-GABA release, but the remotion or chelation of external calcium did. Blockade of Gi, Gs, PLC, PKC, or dopamine D1 receptor signaling proteins did not prevent the effect of GPR55 on release. However, the activation of GPR55 stimulated [ H]-cAMP accumulation and PKA activity. Intranigral unilateral injection of LPI induces contralateral turning. This turning was prevented by CID16020046, cannabidiol, and bicuculline but not by SCH 23390. Our data indicate that presynaptic GPR55 receptors stimulate [ H]-GABA release at striato-nigral terminals through [ H]-cAMP production and stimulate motor behavior.
纹状体中型棘突神经元表达 GPR55 受体的 mRNA 和蛋白，这些受体可刺激神经递质释放；因此，GPR55 可能被运送到黑质纹状体投射区，在那里它可能调节 GABA 释放和运动行为。在这里，我们研究了 GPR55 受体在纹状体-黑质末梢的存在、它们对 GABA 释放的调节、它们的信号通路以及它们对运动活动的影响。通过双重免疫组织化学，我们发现 GPR55 蛋白和 P 物质在背侧纹状体中的共定位。在大鼠黑质切片中，GPR55 激动剂 LPI 和 O-1602 以剂量依赖性方式刺激由高 K 去极化诱导的 [ H]-GABA 释放。拮抗剂 CID16020046 和大麻二酚以剂量依赖性方式阻止激动剂的刺激。GPR55 对黑质 [ H]-GABA 释放的影响被用海人藻酸处理纹状体造成的损伤所阻止，这伴随着黑质突触小体中 GPR55 蛋白的减少，表明受体位于突触前。用 thapsigargin 耗尽细胞内 Ca 库不会阻止 LPI 对 [ H]-GABA 释放的影响，但去除或螯合外部钙可以。阻断 Gi、Gs、PLC、PKC 或多巴胺 D1 受体信号蛋白并不能阻止 GPR55 对释放的影响。然而，GPR55 的激活刺激了 [ H]-cAMP 的积累和 PKA 的活性。黑质内单侧注射 LPI 诱导对侧转动。这种转动被 CID16020046、大麻二酚和 Bicuculline 阻止，但不受 SCH 23390 的影响。我们的数据表明，突触前 GPR55 受体通过 [ H]-cAMP 的产生刺激纹状体-黑质末梢的 [ H]-GABA 释放，并刺激运动行为。
