Endothelin- and sarafotoxin-induced receptor-mediated calcium mobilizationin a clonal murine osteoblast-like cell line, MC3T3-E1/B

Previous studies have demonstrated that, in osteoblast-like MC3T3-E1 cells, various endothelin peptides and their homologous sarafotoxins generate pro staglandin E-2 (PGE(2)) release through an ETA receptor subtype. In this st udy, biphasic Ca2+ signals elicited with endothelin (ET)-1, ET-2, ET-3, bet a -ET, S6a1, and S6b (ET/S6) were measured by microspectrofluorimetric meth ods in cell suspensions loaded with Fura-2 acetoxymethylester (Fura-2 AM). Phospholipase C (PLC)-dependent calcium activation mechanisms seem to be in volved. We found evidence of Ca2+ release from thapsigargin-sensitive and n on-thapsigargin-sensitive intracellular Ca2+ stores as well as Ca2+ transme mbrane inflow through multiple voltage-independent and Ni2+-sensitive catio n channels, Using an ET, receptor antagonist, BQ-123, we showed that this r eceptor was coupled to Ca2+ mobilization, All agonists tested, except S6c t an ETB-receptor-specific agonist) induced receptor desensitization. Our res ults demonstrate that the ET/S6-induced Ca2+ signaling pathway is mediated via an ETA-receptor subtype in MC3T3-E1/B cells. (C) 2001 by Elsevier Scien ce Inc. All rights reserved.