Proton-sensing G protein-coupled receptor mobilizes calcium in human synovial cells.
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 Ca(2+) 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 Ca(2+) mobilization by demonstrating 1) dependence on the integrity of the intracellular Ca(2+) store, 2) independence from extracellular Ca(2+), 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 Ca(2+) 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.
Christensen
Burgess N
BN
Dept. of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555-1043, USA.
Kochukov
Mikhail
M
McNearney
Terry A
TA
Taglialatela
Giulio
G
Westlund
Karin N
KN
D000143:Acids / Q000378:metabolism*; D001168:Arthritis / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D005110:Extracellular Space / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006147:Guanine / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018408:Patch-Clamp Techniques; D011522:Protons; D018102:Receptors, Leukotriene B4; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D012509:Sarcoma; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*
D000143:Acids; C513240:LTB4R protein, human; D011522:Protons; D018102:Receptors, Leukotriene B4; D018048:Receptors, Purinergic P2; D006147:Guanine; D002118:Calcium