TY - JOUR
T1 - The atypical antipsychotic, olanzapine, potentiates ghrelin-induced receptor signaling
T2 - An in vitro study with cells expressing cloned human growth hormone secretagogue receptor
AU - Tagami, Keita
AU - Kashiwase, Yohei
AU - Yokoyama, Akinobu
AU - Nishimura, Hitomi
AU - Miyano, Kanako
AU - Suzuki, Masami
AU - Shiraishi, Seiji
AU - Matoba, Motohiro
AU - Ohe, Yuichiro
AU - Uezono, Yasuhito
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid for Cancer Research for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan , Grants-in-Aid for Scientific Research (C) ( 24590740 , 26462387 , 25462442 , 23592299 , 15K08686 ) and Young Scientists (B) ( 25860199 ) from the Japan Society for the Promotion of Science , the National Cancer Center Research and Development Fund ( 23-A-29 ) and the Research Project for Improving Quality in Healthcare and Collecting Scientific Evidence on Integrative Medicine ( 15lk0310003h0001 ) from the Japan Agency for Medical Research and Development, AMED . This work was also supported in part by grants from the Foundation for Promotion of Cancer Research in Japan and Tsumura & Co .
Publisher Copyright:
© 2015 Elsevier Ltd
PY - 2016/8/1
Y1 - 2016/8/1
N2 - The growth hormone secretagogue receptor (GHS-R) belongs to Gαq-coupled G protein-coupled receptor (GPCR) that mediates growth hormone release, food intake, appetite, glucose metabolism and body composition. Ghrelin has been identified as an endogenous ligand for GHS-R, and it is the only orexigenic peptide found in the peripheral organs. Olanzapine, an atypical antipsychotic agent that binds to and inhibits the activation of GPCR for several neurotransmitters, has metabolic side effects such as excessive appetite and weight gain. Recently, studies have revealed that the orexigenic mechanism of olanzapine is mediated via GHS-R signaling, although the precise mechanisms have not been clarified. In this study, we investigated the effect of olanzapine on ghrelin-mediated GHS-R signaling by using an electrical impedance-based receptor biosensor assay system (CellKey™). Olanzapine at concentrations of 10− 7 and 10− 6 mol/L enhanced ghrelin-induced (10− 10–10− 8 mol/L) GHS-R activation. A Ca2 + imaging assay revealed that olanzapine (10− 7 and 10− 6 mol/L) enhanced ghrelin (10− 7 M)-induced GHS-R activity. In contrast, haloperidol (an antipsychotic agent) failed to enhance this ghrelin-mediated GHS-R activation, as demonstrated by both the CellKey™ and Ca2 + imaging assays. Together, these results suggest that olanzapine, but not haloperidol, promotes appetite by enhancing ghrelin-mediated GHS-R signaling.
AB - The growth hormone secretagogue receptor (GHS-R) belongs to Gαq-coupled G protein-coupled receptor (GPCR) that mediates growth hormone release, food intake, appetite, glucose metabolism and body composition. Ghrelin has been identified as an endogenous ligand for GHS-R, and it is the only orexigenic peptide found in the peripheral organs. Olanzapine, an atypical antipsychotic agent that binds to and inhibits the activation of GPCR for several neurotransmitters, has metabolic side effects such as excessive appetite and weight gain. Recently, studies have revealed that the orexigenic mechanism of olanzapine is mediated via GHS-R signaling, although the precise mechanisms have not been clarified. In this study, we investigated the effect of olanzapine on ghrelin-mediated GHS-R signaling by using an electrical impedance-based receptor biosensor assay system (CellKey™). Olanzapine at concentrations of 10− 7 and 10− 6 mol/L enhanced ghrelin-induced (10− 10–10− 8 mol/L) GHS-R activation. A Ca2 + imaging assay revealed that olanzapine (10− 7 and 10− 6 mol/L) enhanced ghrelin (10− 7 M)-induced GHS-R activity. In contrast, haloperidol (an antipsychotic agent) failed to enhance this ghrelin-mediated GHS-R activation, as demonstrated by both the CellKey™ and Ca2 + imaging assays. Together, these results suggest that olanzapine, but not haloperidol, promotes appetite by enhancing ghrelin-mediated GHS-R signaling.
KW - Anorexia
KW - Appetite
KW - Ca imaging assay
KW - CellKey™ system
KW - Ghrelin
KW - Growth hormone secretagogue receptor
KW - Haloperidol
KW - Olanzapine
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U2 - 10.1016/j.npep.2015.12.010
DO - 10.1016/j.npep.2015.12.010
M3 - Article
C2 - 26775231
AN - SCOPUS:84953432534
SN - 0143-4179
VL - 58
SP - 93
EP - 101
JO - Neuropeptides
JF - Neuropeptides
ER -