Rikkunshito and isoliquiritigenin counteract 5-HT-induced 2C receptor-mediated activation of pro-opiomelanocortin neurons in the hypothalamic arcuate nucleus

• Published in: Neuropeptides (Edinburgh) 2013-08, Vol.47 (4), p.225-230
• Main Authors: Arai, Takeshi, Maejima, Yuko, Muroya, Shinji, Yada, Toshihiko
• Format: Article
• Language: English
• Subjects: 5-HT2C receptor; 5-Hydroxytryptamine; Advanced Basic Science; Animals; Anorexia; Anorexia nervosa; Arcuate nucleus; Arcuate Nucleus of Hypothalamus - drug effects; Arcuate Nucleus of Hypothalamus - metabolism; Calcium - metabolism; Calcium Signaling - drug effects; Chalcones - pharmacology; Drugs, Chinese Herbal - pharmacology; Endocrinology & Metabolism; Enzyme Inhibitors - pharmacology; Male; Neurons - metabolism; Pro-opiomelanocortin; Pro-Opiomelanocortin - metabolism; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT2C - metabolism; Rikkunshito; Serotonin - pharmacology
• ISSN: 0143-4179; 1532-2785
• DOI: 10.1016/j.npep.2013.05.004

Abstract Anorexia deteriorates the quality of life in patients with anorexia nervosa, stress disorders, gastrointestinal disorders, and cancer. Pro-opiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (ARC), serotonin (5-HT) and its 2C receptor (5-HT2CR) are implicated in anorexia. Rikkunshito, a traditional Japanese medicine, has been used to treat anorexia and gastrointestinal disorders. The present study aimed to clarify whether rikkunshito influences the 5-HT action on ARC POMC neurons. We isolated single neurons from the ARC of adult rats and measured cytosolic Ca2+ concentration ([Ca2+ ]i ) by fura-2 microfluorometry combined with immunocytochemical identification of POMC neurons. Administration of 5-HT increased [Ca2+ ]i in ARC neurons, and 80% of the 5-HT-responsive neurons were immunoreactive to POMC. Rikkunshito concentration-dependently and 5-HT2CR antagonist SB242084 significantly suppressed 5-HT-induced [Ca2+ ]i increases. The rikkunshito-suppressed neurons highly overlapped SB242084-suppressed neurons. Isoliquiritigenin, an ingredient of rikkunshito, suppressed 5-HT-induced [Ca2+ ]i increases to a lesser extent than rikkunshito. These results demonstrate that rikkunshito counteracts 5-HT-induced 5-HT2CR-mediated Ca2+ signaling in ARC POMC neurons, and that isoliquiritigenin may serve as an active component of rikkunshito. The ability of rikkunshito to antagonize 5-HT action in ARC POMC neurons could underlie the rikkunshito’s action to attenuate anorexia induced by excessive 5-HT release and/or action associated with psychiatric diseases, gastrointestinal disorders, cancer, and anti-cancer medicines.