Endothelin-1 activates ET(A) receptors to increase intracellular calcium in model sensory neurons.
Endothelin-1 (ET-1) induces endothelin-A (ETA) receptor-mediated pain and selective excitation of nociceptors. Here we studied ET-1-induced changes in intracellular calcium (Ca2+in) in Fura-2 loaded mouse neuroblastoma-rat dorsal root ganglion hybrid cells (ND7/104). ET-1 (1-400 nM) induced concentration-dependent, transient increases in Ca2+in, probably of intracellular 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, KI = 7 nM). No inhibition of the calcium response was observed with the selective ETB antagonist, BQ-788 (10-1000 nM). These results demonstrate that ET-1 induces dose- and ETA receptor-dependent release of Ca2+in in nociceptor-like neurons, and permit further examination of the pathways that underlie ET-1-induced pain signaling.
Zhou
Q L
QL
Molecular Neurobiology of Pain, and 1Sensory Neurophysiology Laboratories of the Pain Research Center, Department of Anesthesiology, Perioperative and Pain Management, Brigham and Women's Hospital, Boston, MA 02115, USA.
Strichartz
G
G
Davar
G
G
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D005456:Fluorescent Dyes; D005470:Fluorometry; D016257:Fura-2; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009447:Neuroblastoma; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000819:agonists / Q000378:metabolism*
D000959:Antihypertensive Agents; D015220:Calcium Channels; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D005456:Fluorescent Dyes; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D002118:Calcium; D016257:Fura-2