title: Dopamine D1 receptor signaling system regulates ryanodine receptor expression after intermittent exposure to methamphetamine in primary cultures of midbrain and cerebral cortical neurons.
abstract: Regulatory mechanisms of ryanodine receptor (RyR) expression are not well known, although methamphetamine (METH) has been reported to up-regulate RyRs in mouse brain. This study investigate regulatory mechanisms of RyR expression by dopaminergic system using the midbrain and cerebral cortical neurons in primary culture intermittently exposed to METH and dopamine receptor (DR) agonists (1 h/day, for 3 days). Intermittent METH (10 μM) exposure enhanced RyR-1 and -2 proteins and their mRNA, but not RyR-3 expression in the both types of the neurons. These METH-induced increases of RyR proteins and their mRNA were dose-dependently blocked by SCH23390 (a selective D(1) DR antagonist), but not a D(2)DR antagonist sulpiride, suggesting a regulatory role of D(1)DRs in RyR expression by METH in these neurons. In cerebral cortical neurons, intermittent SKF82958 (a selective D(1)DR agonist) exposure increased RyR-1 and -2 proteins and their mRNA, whereas quinpirole (a selective D(2)DR agonist) showed no effects. KT5720, a protein kinase A inhibitor, dose-dependently attenuated the METH-stimulated RyR-1 and -2 expressions in cerebral cortical neurons. METH significantly increased phosphorylation of cAMP-response element-binding protein, which was completely suppressed by SCH23390. These results indicate that RyR-1 and -2 expressions are regulated by D(1)DRs via the signal transduction linked to D(1)DRs.
authors.affiliation: Department of Pharmacology, Kawasaki Medical School, Matsushima, Kurashiki, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kurokawa
authors.forename: Koji
authors.initials: K
authors.lastname: Mizuno
authors.forename: Emi
authors.initials: E
authors.lastname: Kiyokage
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shibasaki
authors.forename: Kazunori
authors.initials: K
authors.lastname: Toida
authors.forename: Seitaro
authors.initials: S
authors.lastname: Ohkuma
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000166:cytology; D003609:Dactinomycin / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D008636:Mesencephalon / Q000166:cytology; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D011247:Pregnancy; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D001552:Benzazepines; D002227:Carbazoles; D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D011500:Protein Synthesis Inhibitors; D011758:Pyrroles; D017447:Receptors, Dopamine D1; D019837:Ryanodine Receptor Calcium Release Channel; C534628:SCH 23390; D003609:Dactinomycin; D019257:Quinpirole; D008694:Methamphetamine; C057416:KT 5720; C071262:SK&F 82958