Endothelin-1 activates ETA receptors to increase intracellular calcium in model sensory neurons

Endothelin-1 (ET-1) induces enclothelin-A (ETA) receptormediated pain and s elective excitation of nociceptors. Here we studied ET-1-induced changes in intracellular calcium (Ca-in(2+)) in Fura-2 loaded mouse neuroblastoma-rat dorsal root ganglion hybrid cells (ND7/104). ET-1 (1-400 nM) induced conce ntration-dependent, transient increases in Ca-in(2+), probably of intracell ular source. Responses to repeated application declined with increasing ET- 1 concentration, implying receptor desensitization. Treatment of cells with the selective ETA, receptor antagonist, BQ-123, produced a dose-dependent inhibition of the response that was 20% of ET-1 alone (IC50 = 20 nM, K-1 = 7 nM). No inhibition of the calcium response was observed with the selectiv e ETB antagonist, BQ-788 (10-1000 nM). These results demonstrate that ET-I induces dose- and ETA receptor-dependent release of Ca2+ in in nociceptor-l ike neurons, and permit further examination of the pathways that underlie E T-1-induced pain signaling. NeuroReport 12:3853-3857 (C) 2001 Lippincott Wi lliams & Wilkins.