The atypical antipsychotic, olanzapine, potentiates ghrelin-induced receptor signaling: An in vitro study with cells expressing cloned human growth hormone secretagogue receptor

被引:21
|
作者
Tagami, Keita [1 ,2 ,3 ]
Kashiwase, Yohei [1 ,4 ]
Yokoyama, Akinobu [1 ,4 ]
Nishimura, Hitomi [1 ,4 ]
Miyano, Kanako [1 ]
Suzuki, Masami [1 ]
Shiraishi, Seiji [1 ]
Matoba, Motohiro [5 ]
Ohe, Yuichiro [3 ,6 ]
Uezono, Yasuhito [1 ,7 ,8 ]
机构
[1] Natl Canc Ctr, Res Inst, Div Canc Pathophysiol, Chuo Ku, 5-1-1 Tsukiji, Tokyo 1040045, Japan
[2] Natl Canc Ctr Hosp East, Dept Palliat Med, 6-5-1 Kashiwanoha, Kashiwa, Chiba 2778577, Japan
[3] Juntendo Univ, Grad Sch Med, Div Adv Clin Res Canc, Bunkyo Ku, 2-1-1 Hongou, Tokyo 1138421, Japan
[4] Tokyo Univ Sci, Div Mol Pathol & Metab Dis, Fac Pharmaceut Sci, 2641 Yamazaki, Noda, Chiba 2780022, Japan
[5] Japanese Red Cross Med Ctr, Dept Palliat Med, Shiguya Ku, 4-1-22 Hiroo, Tokyo 1508935, Japan
[6] Natl Canc Ctr, Dept Thorac Oncol, Chuo Ku, 5-1-1 Tsukiji, Tokyo 1040045, Japan
[7] Natl Canc Ctr, Div Support Care Res, Natl Canc Ctr Exploratory Oncol Res & Clin Trial, Chuo Ku, 5-1-1 Tsukiji, Tokyo 1040045, Japan
[8] Natl Canc Ctr, Innovat Ctr Support Palliat & Psychosocial Care, 5-1-1 Tsukiji, Tokyo 1040045, Japan
基金
日本学术振兴会;
关键词
Anorexia; Appetite; Ca2+ imaging assay; CellKey (TM) system; Ghrelin; Growth hormone secretagogue receptor; Haloperidol; Olanzapine; PROTEIN-COUPLED RECEPTORS; INDUCED WEIGHT-GAIN; BODY-WEIGHT; CANCER CACHEXIA; FOOD-INTAKE; 2ND-GENERATION ANTIPSYCHOTICS; INDUCED HYPERPHAGIA; INSULIN-SECRETION; ANOREXIA-CACHEXIA; DOUBLE-BLIND;
D O I
10.1016/j.npep.2015.12.010
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The growth hormone secretagogue receptor (GHS-R) belongs to G alpha q-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 (TM)). Olanzapine at concentrations of 10(-7) and 10(-6) mol/L enhanced ghrelin-induced (10(-16)-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 (TM) and Ca2+ imaging assays. Together, these results suggest that olanzapine, but not haloperidol, promotes appetite by enhancing ghrelin-mediated GHS-R signaling. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码:93 / 101
页数:9
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