Risperidone reduces mRNA expression levels of Sulfonylurea Receptor 1 and TASK1 in PC12 cells.
Electrophysiological and immunohistochemical studies have demonstrated that glucose-sensing neurons in the hypothalamus contain both ATP-sensitive K(+) (K(ATP)) and tandem-pore K(+) (TASK1 and TASK3) channels and that glucose-induced depolarization or hyperpolarization of these neurons function as an important link between glucose-excited or glucose-inhibited neurons and feeding behavior. Medication with atypical antipsychotics increases the appetite of schizophrenic patients and thus causes increases in body weight. Therefore, the present study investigates mRNA expression levels of the genes encoding the components of these K(+) channel subsets in PC12 cells cultured with risperidone (an atypical antipsychotic) and in the hypothalami of rats subcutaneously injected for 21 consecutive days with 0.1 or 0.01 mg/kg/day of risperidone. The mRNA expression levels of various genes were not obviously altered in rat hypothalami. However, the mRNA expression levels for sulfonylurea receptor 1, a component affording nucleotide-binding folds to K(ATP) channels, and TASK1 were down-regulated in PC12 cells cultured with 50 microM risperidone for 24h, but the amount of intracellular ATP in these cells was not affected by the drug. Collectively, these results indicate that the amplitude of the current through these K(+) channels in PC12 cells might be modulated as a pharmacological effect of risperidone.
Ota
Miyuki
M
Department of Neuropsychiatry, Tosei General Hospital, Seto 489-8642, Japan.
Nakashima
Akira
A
Kaneko
Yoko S
YS
Mori
Keiji
K
Takami
Goro
G
Ota
Akira
A
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D016716:PC12 Cells / Q000187:drug effects; D024661:Potassium Channels, Inwardly Rectifying; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011955:Receptors, Drug; D018967:Risperidone / Q000494:pharmacology*; D064233:Sulfonylurea Receptors
D018528:ATP-Binding Cassette Transporters; D018492:Dopamine Antagonists; D005947:Glucose; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009419:Nerve Tissue Proteins; D024661:Potassium Channels, Inwardly Rectifying; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; D011955:Receptors, Drug; D018967:Risperidone; D064233:Sulfonylurea Receptors; C420132:potassium channel subfamily K member 3