Characterization of molecular mechanisms of extracellular acidification-induced intracellular Ca2+ increase in LβT2 cells

Biochem Biophys Res Commun. 2019 Oct 1;517(4):636-641. doi: 10.1016/j.bbrc.2019.07.083. Epub 2019 Aug 7.

Abstract

Extracellular acidification regulates endocrine cell functions. Ovarian cancer G protein-coupled receptor 1 (OGR1), also known as GPR68, is a proton-sensing G protein-coupled receptor and is activated by extracellular acidification, resulting in the activation of multiple intracellular signaling pathways. In the present study, we found that OGR1 was expressed in some gonadotropic cells in rat anterior pituitary and in LβΤ2 cells, which are used as a model of gonadotropic cells. When we reduced extracellular pH, a transient intracellular Ca2+ increase was detected in LβT2 cells. The Ca2+ increase was inhibited by a Gq/11 inhibitor and Cu2+, which is known as an OGR1 antagonist. We also found that extracellular acidification enhanced GnRH-induced Gaussia luciferase secretion from LβT2 cells. These results suggest that OGR1 may play a role in the regulation of gonadotropic cell function such as its hormone secretion.

Keywords: Extracellular acidification; Gaussia luciferase; Intracellular Ca(2+); LβT2; OGR1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acids / metabolism*
  • Animals
  • Calcium / metabolism*
  • Cells, Cultured
  • Extracellular Space / metabolism*
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
  • Humans
  • Intracellular Space / metabolism*
  • Luciferases / metabolism
  • Luteinizing Hormone / metabolism
  • Pituitary Gland, Anterior / cytology
  • Rats
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / metabolism
  • Time Factors

Substances

  • Acids
  • LOC102553138 protein, rat
  • Receptors, G-Protein-Coupled
  • Luteinizing Hormone
  • Luciferases
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Calcium