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Opposite regulation by L-DOPA receptor GPR143 of the long and short forms of the dopamine D2 receptors.
- Source :
-
Journal of pharmacological sciences [J Pharmacol Sci] 2024 Oct; Vol. 156 (2), pp. 77-81. Date of Electronic Publication: 2024 Jul 30. - Publication Year :
- 2024
-
Abstract
- Dopamine (DA) D2 receptors (D2Rs) have 2 isoforms, a long form (D2L) and a short form (D2S). D2L is predominantly postsynaptic in the striatal medium spiny neurons and cholinergic interneurons. D2S is principally presynaptic autoreceptors in the nigrostriatal DA neurons. Recently, we demonstrated that L-3,4-dihydroxyphenylalanine (L-DOPA) augments D2L function through the coupling between D2L and GPR143, a receptor of L-DOPA that was originally identified as the gene product of ocular albinism 1. Here we show that GPR143 modifies the functions of D2L and D2S in an opposite manner. Haloperidol-induced catalepsy was attenuated in DA neuron-specific Gpr143 gene-deficient (Dat-cre;Gpr143 <superscript>flox/y</superscript> ) mice, compared with wild-type (Wt) mice. Haloperidol increased in vivo DA release from the dorsolateral striatum, and this increase was augmented in Gpr143 <superscript>-/y</superscript> mice compared with Wt mice. A D2R agonist quinpirole-induced increase in the phosphorylation of GSK3β(pGSK3β(S9)) was enhanced in Chinese hamster ovary (CHO) cells coexpressing D2L and GPR143 compared with cells expressing D2L alone, while it was suppressed in cells coexpressing D2S and GPR143 compared with D2S alone, suggesting that GPR143 differentially modifies D2R functions depending on its isoforms of D2L and D2S.<br />Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists.<br /> (Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
CHO Cells
Corpus Striatum metabolism
Male
Membrane Glycoproteins metabolism
Membrane Glycoproteins genetics
Protein Isoforms metabolism
Protein Isoforms genetics
Mice
Levodopa pharmacology
Catalepsy chemically induced
Catalepsy genetics
Catalepsy metabolism
Mice, Inbred C57BL
Phosphorylation
Receptors, G-Protein-Coupled metabolism
Receptors, G-Protein-Coupled genetics
Receptors, G-Protein-Coupled physiology
Quinpirole pharmacology
Dopaminergic Neurons metabolism
Glycogen Synthase Kinase 3 beta metabolism
Receptors, Dopamine D2 metabolism
Receptors, Dopamine D2 genetics
Haloperidol pharmacology
Cricetulus
Dopamine metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1347-8648
- Volume :
- 156
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of pharmacological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 39179337
- Full Text :
- https://doi.org/10.1016/j.jphs.2024.07.009