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

Keita Tagami, Yohei Kashiwase, Akinobu Yokoyama, Hitomi Nishimura, Kanako Miyano, Masami Suzuki, Seiji Shiraishi, Motohiro Matoba, Yuichiro Ohe, Yasuhito Uezono

研究成果: Article査読

15 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)93-101
ページ数9
ジャーナルNeuropeptides
58
DOI
出版ステータスPublished - 2016 8 1
外部発表はい

ASJC Scopus subject areas

  • Endocrinology
  • Neurology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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