Proton-sensing G protein-coupled receptor mobilizes calcium in human synovial cells

Burgess N. Christensen, Mikhail Kochukov, Terry A. McNearney, Giulio Taglialatela, Karin N. Westlund

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Lowered extracellular pH in a variety of tissues is associated with increased tissue destruction and initiation of inflammatory processes. Although the acid-sensing receptors described previously are ion channels, we describe a G protein-coupled proton-sensitive receptor that stimulates Ca2+ release from intracellular stores in a tumor-derived synoviocyte cell line (SW982) and in primary cultures of human synovial cells from patients with inflammatory arthropathies. We established a link between proton-dependent receptor activation and intracellular Ca2+ mobilization by demonstrating 1) dependence on the integrity of the intracellular Ca 2+ store, 2) independence from extracellular Ca2+, and 3) proton-induced production of inositol phosphate and 4) by abolishing the effect with GTPase inhibitors. We propose that this G protein-coupled acid-sensing receptor linked to intracellular Ca2+ mobilization in synoviocytes can contribute to downstream inflammatory and cellular proliferative processes in synovial fibroblasts. The acid-sensing receptor has distinct characteristics as a metabotropic G protein-coupled receptor on human synoviocytes in this emerging new class of receptors.

Original languageEnglish (US)
Pages (from-to)C601-C608
JournalAmerican Journal of Physiology - Cell Physiology
Volume289
Issue number3 58-3
DOIs
StatePublished - Sep 2005

Keywords

  • Acid-sensing receptor
  • Arthritis
  • Calcium imaging
  • Synoviocytes

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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