PMID:22504960

Citation	Kurokawa, K, Mizuno, K and Ohkuma, S (2012) Increase of ryanodine receptors by dopamine D1 receptors is negatively regulated by γ-aminobutyric acid type B receptors in primary cultures of mouse cerebral cortical neurons. J. Neurosci. Res. 90:1626-38
Abstract	Although upregulation of ryanodine receptor (RyR)-1 and -2 is mediated through the activation of dopamine D1 receptors (D1DRs) in the development of psychostimulant-induced place preference, little is known about how such increased expressions of RyRs are negatively regulated. This study investigated negative regulatory mechanisms of increase of RyR-1 and -2 expression by D1DR stimulation with its full agonist, SKF82958 or A 68930, using cultures of mouse cerebral cortical neurons. Sustained exposure to SKF82958 or A 68930 of the neurons increased RyR-1 and -2 proteins in a dose- and time-dependent-manner. The SKF82958-induced increases of RyR-1 and -2 proteins were significantly suppressed by SCH23390 (a selective D1DR antagonist). In addition, the SKF82958- or A 68930-induced increases of RyR-1 and -2 proteins were completely abolished by baclofen (a selective γ-aminobutyric acid type B [GABA(B)] receptor agonist), whereas muscimol (an agonist specific to GABA(A) receptors) had no effect. SKF82958 or A 68930 significantly increased intracellular cAMP level, which was completely suppressed by baclofen. Furthermore, sustained exposure to phorbol 12,13-dibutyrate, a protein kinase C activator, did not change the expression of RyR-1 or -2 proteins. Immunohistochemical study showed colocalizaton of immunoreactivities for three types of proteins, D1DRs and GABA(B) receptor R1 and R2 subunits in the same neuronal bodies, suggesting that the neurochemical changes induced by the activation of D1DRs and GABA(B) receptors occur in the same neurons. These results indicate that RyR-1 and -2 expression facilitated by D1DR stimulation are negatively regulated by GABA(B) receptor via suppression of cAMP production.
Links	PubMed Online version:10.1002/jnr.23058
Keywords	Animals; Blotting, Western; Cells, Cultured; Cerebral Cortex/drug effects; Cerebral Cortex/metabolism; Cyclic AMP/metabolism; Dopamine Agonists/pharmacology; Dopamine Antagonists/pharmacology; GABA Agonists/pharmacology; Immunohistochemistry; Mice; Neurons/drug effects; Neurons/metabolism; Receptors, Dopamine D1/metabolism; Receptors, GABA-B/metabolism; Ryanodine Receptor Calcium Release Channel/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:GABR1		GO:0007214: gamma-aminobutyric acid signaling pathway	ECO:0000314:		P		Figure 6B Intracellular cAMP level was completely suppressed by baclofen.	complete CACAO 5749
MOUSE:GABR1		GO:0004965: G-protein coupled GABA receptor activity	ECO:0000314:		F		Figure 6B.	complete CACAO 5750
MOUSE:GABR2		GO:0007214: gamma-aminobutyric acid signaling pathway	ECO:0000314:		P		Figure 6B	complete CACAO 5751
MOUSE:GABR2		GO:0004965: G-protein coupled GABA receptor activity	ECO:0000314:		F		Figure 6B	complete CACAO 5752

References

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