Endothelin-stimulated Ca2+ signaling and endothelin receptor expression are decreased by parathyroid hormone treatment in UMR-106 osteoblastic osteosarcoma cells

D. E. Semler, D. L. Morris, P. H. Stern*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Modulation of endothelin (ET-1)-induced [Ca2+](i) transients and receptor expression by parathyroid hormone (PTH) was studied in UMR-106 osteoblastic osteosarcoma cells. Ca2+ signaling was assessed with Fura-2, and ET receptor mRNA expression was determined using ET(A) - and ET(B) -specific primers and RT-PCR amplification. ET-1 binding in UMR-106 cell membranes was also measured. PTH pretreatment for 8 h decreased the [Ca2+](i) transients elicited by ET-1 and by the ET(B)-selective agonist sarafotoxin 6c (S6c). When ET(B) receptors were desensitized by pretreatment with S6c or blocked with the ET(B)-selective antagonist BQ-788, the remaining ET(A) component of the signal was also decreased by PTH pretreatment. In contrast, [Ca2+](i) transients elicited by PGF(2α) and ionomycin were increased following PTH pretreatment, indicating that the effect of PTH to decrease ET-1-stimulated transients was selective. PTH pretreatment also decreased [125I]ET-1 binding and ET(A) and ET(B) mRNA, with maximal effects at approximately 8 h. ET-1 was not detectable in medium from either control or PTH treated UMR-106 cultures, suggesting that the decreased expression of ET receptors was not due to enhanced ET production and subsequent homologous desensitization. The downregulation of ET receptors in osteoblasts by PTH pretreatment may serve as a homeostatic mechanism in bone. (C) 2000 Harcourt Publishers Ltd.

Original languageEnglish (US)
Pages (from-to)55-64
Number of pages10
JournalCell Calcium
Volume28
Issue number1
DOIs
StatePublished - 2000

Funding

Supported by research grant AR-11262 from the National Institutes of Health.

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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