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The Inhibition of TREK-1 K+ Channels via Multiple Compounds Contained in the Six Kamikihito Components, Potentially Stimulating Oxytocin Neuron Pathways.
Miyano, Kanako; Nonaka, Miki; Sakamoto, Masahiro; Murofushi, Mika; Yoshida, Yuki; Komura, Kyoko; Ohbuchi, Katsuya; Higami, Yoshikazu; Fujii, Hideaki; Uezono, Yasuhito.
Afiliación
  • Miyano K; Department of Pain Control Research, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
  • Nonaka M; Department of Dentistry, National Cancer Center Hospital, Tokyo 104-0045, Japan.
  • Sakamoto M; Laboratory of Pharmacotherapeutics, Faculty of Pharmacy, Juntendo University, Chiba 279-0013, Japan.
  • Murofushi M; Department of Pain Control Research, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
  • Yoshida Y; Department of Pain Control Research, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
  • Komura K; Department of Pain Control Research, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
  • Ohbuchi K; Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University, Tokyo 108-8641, Japan.
  • Higami Y; Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
  • Fujii H; Department of Pain Control Research, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
  • Uezono Y; Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University, Tokyo 108-8641, Japan.
Int J Mol Sci ; 25(9)2024 Apr 30.
Article en En | MEDLINE | ID: mdl-38732124
ABSTRACT
Oxytocin, a significant pleiotropic neuropeptide, regulates psychological stress adaptation and social communication, as well as peripheral actions, such as uterine contraction and milk ejection. Recently, a Japanese Kampo medicine called Kamikihito (KKT) has been reported to stimulate oxytocin neurons to induce oxytocin secretion. Two-pore-domain potassium channels (K2P) regulate the resting potential of excitable cells, and their inhibition results in accelerated depolarization that elicits neuronal and endocrine cell activation. We assessed the effects of KKT and 14 of its components on a specific K2P, the potassium channel subfamily K member 2 (TREK-1), which is predominantly expressed in oxytocin neurons in the central nervous system (CNS). KKT inhibited the activity of TREK-1 induced via the channel activator ML335. Six of the 14 components of KKT inhibited TREK-1 activity. Additionally, we identified that 22 of the 41 compounds in the six components exhibited TREK-1 inhibitory effects. In summary, several compounds included in KKT partially activated oxytocin neurons by inhibiting TREK-1. The pharmacological effects of KKT, including antistress effects, may be partially mediated through the oxytocin pathway.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oxitocina / Canales de Potasio de Dominio Poro en Tándem / Neuronas Límite: Animals / Humans Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oxitocina / Canales de Potasio de Dominio Poro en Tándem / Neuronas Límite: Animals / Humans Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza