M. Koolpe et al., ADENOSINE 5'-TRIPHOSPHATE, URIDINE 5'-TRIPHOSPHATE, BRADYKININ, AND LYSOPHOSPHATIDIC ACID INDUCE DIFFERENT PATTERNS OF CALCIUM RESPONSES BYHUMAN ARTICULAR CHONDROCYTES, Journal of orthopaedic research, 16(2), 1998, pp. 217-226
Small calcium-mobilizing inflammatory mediators have been implicated i
n joint pathology. Here we demonstrate that bradykinin, adenosine 5'-t
riphosphate, uridine 5'-triphosphate, and lysophosphatidic acid raise
the intracellular calcium concentration ([Ca2+](i)) in human articular
chondrocytes. Heterologous cross-desensitization experiments showed t
hat the uridine 5'-triphosphate response was abolished by prior treatm
ent with adenosine 5'-triphosphate and, conversely, that the adenosine
5'-triphosphate response was abolished by prior treatment with uridin
e 5'-triphosphate; this indicated competition for the same receptor si
te, whereas bradykinin and lysophasphatidic acid did not compete with
other ligands. Pretreatment with thapsigargin abolished ligand-mediate
d Ca2+ responses but not vice versa; this confirmed that Ca2+ release
occurred from intracellular stores. Single-cell analysis of Fura-2 ace
toxymethyl ester loaded chondrocytes showed mediator-dependent pattern
s of oscillatory Ca2+ changes in a subset of cells when challenged wit
h submaximal concentrations of bradykinin, adenosine 5'-triphosphate,
or uridine 5'-triphosphate in the presence of extracellular Ca2+. Howe
ver, no oscillatory responses were seen after a challenge with lysopho
sphatidic acid. Therefore, although a number of different Ca2+-mobiliz
ing ligands activate chondrocytes, the differences that occur in the t
emporal patterning of Ca2+ responses may result in unique mediator-dep
endent changes in cellular activity.