Aldosterone, STX and amyloid-β1-42 peptides modulate GPER (GPR30) signalling in an embryonic mouse hippocampal cell line (mHippoE-18)

Mol Cell Endocrinol. 2019 Oct 1:496:110537. doi: 10.1016/j.mce.2019.110537. Epub 2019 Aug 9.

Abstract

The GPCR, GPER, mediates many of the rapid, non-genomic actions of 17β-estradiol in multiple tissues, including the nervous system. Controversially, it has also been suggested to be activated by aldosterone, and by the non-steroidal diphenylacrylamide compound, STX, in some preparations. Here, the ability of the GPER agonist, G-1, and aldosterone in the presence of the mineralocorticoid receptor antagonist, eplerenone, to potentiate forskolin-stimulated cyclic AMP levels in the hippocampal clonal cell line, mHippoE-18, are compared. Both stimulatory effects are blocked by the GPER antagonist G36, by PTX, (suggesting the involvement of Gi/o G proteins), by BAPTA-AM, (suggesting they are calcium sensitive), by wortmannin (suggesting an involvement of PI3Kinase) and by soluble amyloid-β peptides. STX also stimulates cyclic AMP levels in mHippoE-18 cells and these effects are blocked by G36 and PTX, as well as by amyloid-β peptides. This suggests that both aldosterone and STX may modulate GPER signalling in mHippoE-18 cells.

Keywords: 17β-Estradiol; Aldosterone; Amyloid-β peptides; Cyclic AMP; G-protein coupled estrogen sensitive receptor (GPER); GPR30; Hippocampus; STX; mHippoE-18 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides / pharmacology*
  • Aldosterone / pharmacology*
  • Amyloid beta-Peptides / pharmacology*
  • Animals
  • Cell Line
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism*
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Mice
  • Peptide Fragments / pharmacology*
  • Receptors, Estrogen / metabolism*
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction / drug effects*

Substances

  • 2-(4-hydroxyphenyl)-3-phenylpent-2-enoic acid (4-(2-dimethylaminoethoxy)phenyl)amide
  • Acrylamides
  • Amyloid beta-Peptides
  • GPER1 protein, mouse
  • Peptide Fragments
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled
  • amyloid beta-protein (1-42)
  • Aldosterone