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Abstract

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 and P H Stern
Journal of Pharmacology and Experimental Therapeutics March 1995, 272 (3) 1052-1058;
D E Semler
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E H Ohlstein
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P Nambi
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C Slater
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P H Stern
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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 ETB-selective agonist sarafotoxin 6c (S6c) elicited rapid calcium transients. Maximally effective concentrations of the ETA-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 ETA/ETB nonselective antagonist PD-142893 (Ac-D-diphenylalanine-Leu-Asp-Ile-Ile-Trp) eliminated the ET-1-stimulated calcium transient. These cells display both ETA and ETB receptors (60:40), as demonstrated by saturation binding experiments with [125I] ET-1 and the ETB 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 ETA and ETB receptors to elicit calcium transients in UMR-106 osteoblastic osteosarcoma cells.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 272, Issue 3
1 Mar 1995
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Abstract

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 and P H Stern
Journal of Pharmacology and Experimental Therapeutics March 1, 1995, 272 (3) 1052-1058;

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Abstract

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 and P H Stern
Journal of Pharmacology and Experimental Therapeutics March 1, 1995, 272 (3) 1052-1058;
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