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RECEPTORS AND SIGNAL TRANSDUCTION

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

Departments of ¹Neuroscience and Cell Biology, ²Internal Medicine, and ³Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas

Submitted 1 February 2005 ; accepted in final form 7 April 2005

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 Ca²⁺ 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.

calcium imaging; synoviocytes; arthritis; acid-sensing receptor

This article has been cited by other articles:

				M. Y. Kochukov, T. A. McNearney, Y. Fu, and K. N. Westlund Thermosensitive TRP ion channels mediate cytosolic calcium response in human synoviocytes Am J Physiol Cell Physiol, September 1, 2006; 291(3): C424 - C432. [Abstract] [Full Text] [PDF]