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

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

Journal of Pharmacology and Experimental Therapeutics 272(3): 1052-1058


ISSN/ISBN: 0022-3565
PMID: 7891315
Accession: 008605248

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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(-DTrp-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 (Glu-9, Ala-11,15) 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.