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Presynaptic nigral GPR55 receptors stimulate [3H]‐GABA release through [3H]‐cAMP production and PKA activation and promote motor behavior

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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… Click to show full abstract

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 [3H]‐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 [3H]‐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 Ca2+ stores with thapsigargin did not prevent the effect of LPI on [3H]‐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 [3H]‐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 [3H]‐GABA release at striato‐nigral terminals through [3H]‐cAMP production and stimulate motor behavior.

Keywords: gaba release; receptors stimulate; gpr55; gpr55 receptors; motor; release

Journal Title: Synapse
Year Published: 2022

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