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

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)93-101
Number of pages9
JournalNeuropeptides
Volume58
DOIs
Publication statusPublished - 2016 Aug 1
Externally publishedYes

Keywords

  • Anorexia
  • Appetite
  • Ca imaging assay
  • CellKey™ system
  • Ghrelin
  • Growth hormone secretagogue receptor
  • Haloperidol
  • Olanzapine

ASJC Scopus subject areas

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

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