P2Y2 receptors are expressed by human osteoclasts of giant cell tumor but do not mediate ATP-induced bone resorption
| Autor: | W.B. Bowler, James A. Gallagher, G. Bilbe, C.J. Dixon, A. Littlewood-Evans |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
medicine.medical_specialty
P2Y receptor Histology Physiology G protein Endocrinology Diabetes and Metabolism Osteoclasts Bone Neoplasms Uridine Triphosphate P2 receptor Biology Bone resorption Receptors Purinergic P2Y2 chemistry.chemical_compound Adenosine Triphosphate Cytosol Nickel Internal medicine Tumor Cells Cultured Extracellular medicine Humans Bone Resorption Receptor In Situ Hybridization Uridine triphosphate Giant Cell Tumor of Bone Receptors Purinergic P2 Affinity Labels Cell biology Endocrinology chemistry Giant cell Calcium |
| Zdroj: | Bone. 22:195-200 |
| ISSN: | 8756-3282 |
| DOI: | 10.1016/s8756-3282(97)00280-9 |
| Popis: | Extracellular nucleotides acting through P2 receptors elicit a range of responses in many cell types. Previously, we have cloned the G-protein coupled P2Y2 receptor from a human osteoclastoma complementary deoxyribonucleic acid (cDNA) library and demonstrated its expression by reverse transcription linked (RT)-PCR and Southern analysis in a number of skeletal tissues, including a purified population of giant cells. In this study we have localized the expression of P2Y2 receptor transcripts to osteoclasts of giant cell tumor of bone by in situ hybridization. In osteoblasts and other cell types, the P2Y2 receptor is coupled to Ins(1,4,5)P 3 -mediated Ca 2+ release from intracellular stores. In this study, the P2Y2 receptor agonists adenosine triphosphate (ATP) and uridine triphosphate (UTP) did not increase cytosolic free calcium concentration ([Ca 2+ ] i ) in giant cells isolated from osteoclastoma, while the G-protein coupled calcium sensing receptor agonist, Ni 2+ , elevated [Ca 2+ ] i in the same cells. These data indicate that P2Y2 receptor transcripts expressed by giant cells are not presented at the surface of cells as functional receptors, or alternatively, functional receptors are coupled to an effector other than [Ca 2+ ] i . ATPγS (10 μmol/L), but not UTP (10 μmol/L), significantly stimulated resorption by an enriched giant cell population. These results indicate that ATP-induced effects on resorption, following direct osteoclastic activation, are mediated by a P2 receptor other than the P2Y2 subtype. Nucleotides, released locally in the bone microenvironment in response to acute trauma or transient physical stress, will interact with a complement of P2 receptors expressed by both osteoclasts and osteoblasts to influence the remodeling process. |
| Databáze: | OpenAIRE |
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