Endothelin-1-evoked calcium transients in UMR-106 osteoblastic osteosarcoma cells are mediated through endothelin-A and endothelin-B receptors

D. E. Semler*, E. H. Ohlstein, P. Nambi, C. Slater, P. H. Stern

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Endothelin (ET) receptor subtypes involved in the modulation of intracellular calcium were studied in UMR-106 osteoblastic osteosarcoma cells. Calcium signaling in UMR-106 cells in suspension was determined with fluo-3-acetoxymethylester fluorescent dye. ET-1 and the ET(B)-selective agonist sarafotoxin 6c (S6c) elicited rapid calcium transients. Maximally effective concentrations of the ET(A)-selective antagonist BQ-123 [Cyclo(-D- Trp-D-Asp-Pro-D-Val-Leu)] attenuated ET-1-evoked calcium transients by only 50%. BQ-123 had no effect on S6c-stimulated transients. ET-1 and S6c showed homologous desensitization on repeated administration. Pretreatment with ET- 1 completely eliminated S6c-evoked calcium transients, whereas S6c pretreatment only partially (50%) attenuated the calcium transient evoked by ET-1. Joint pretreatment with S6c and BQ-123 or pretreatment with the ET(A)/ET(B) nonselective antagonist PD-142893 (Ac-D-diphenylalanine-Leu-Asp- Ile-Ile-Trp) eliminated the ET-1-stimulated calcium transient. These cells display both ET(A) and ET(B) receptors (60:40), as demonstrated by saturation binding experiments with [125I] ET-1 and the ET(B) specific agonist, [125I] IRL-1620 (Suc [Glu9, Ala11,15] endothelin-1 [8-21]). This was further confirmed by competition binding experiments using [125I] ET-1 and subtype-selective ligands S6c and BQ-123. These data indicate that ET-1 interacts with both ET(A) and ET(B) receptors to elicit calcium transients in UMR-106 osteoblastic osteosarcoma cells.

Original languageEnglish (US)
Pages (from-to)1052-1058
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume272
Issue number3
StatePublished - 1995

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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