Adenosine 5′-triphosphate, uridine 5′-triphosphate, bradykinin, and lysophosphatidic acid induce different patterns of calcium responses by human articular chondrocytes
✍ Scribed by Mitchell Koolpe; Juan J. Rodrigo; Hilary P. Benton
- Book ID
- 102915783
- Publisher
- Elsevier Science
- Year
- 1998
- Tongue
- English
- Weight
- 968 KB
- Volume
- 16
- Category
- Article
- ISSN
- 0736-0266
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✦ Synopsis
Abstract
Small calcium‐mobilizing inflammatory mediators have been implicated in joint pathology. Here we demonstrate that bradykinin, adenosine 5′‐triphosphate, uridine 5′‐triphosphate, and lysophosphatidic acid raise the intracellular calcium concentration ([Ca^2+^]~i~) in human articular chondrocytes. Heterologous cross‐desensitization experiments showed that the uridine 5′‐triphosphate response was abolished by prior treatment with adenosine 5′‐triphosphate and conversely, that the adenosine 5′‐triphosphate response was abolished by prior treatment with uridine 5′‐triphosphate: this indicated competition for the same receptor site, whereas bradykinin and lysophosphatidic acid did not compete with other ligands. Pretreatment with thapsigargin abolished ligand‐mediated Ca^2+^ responses but not vice versa: this confirmed that Ca^2+^ release occurred from intracellular stores. Single‐cell analysis of Fura‐2 acetoxymethyl ester loaded chondrocytes showed mediator‐dependent patterns of oscillatory Ca^2+^ changes in a subset of cells when challenged with submaximal concentrations of bradykinin, adenosine 5′‐triphosphate, or uridine 5′‐triphosphate in the presence of extracellular Ca^2+^. However, no oscillatory responses were seen after a challenge with lysophosphatidic acid. Therefore, although a number of different Ca^2+^‐mobilizing ligands activate chondrocytes, the differences that occur in the temporal patterning of Ca^2+^ responses may result in unique mediator‐dependent changes in cellular activity.