Abstract
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.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Antihypertensive Agents / pharmacology
-
Calcium / metabolism*
-
Calcium Channels / drug effects
-
Calcium Channels / metabolism
-
Calcium Signaling / drug effects
-
Calcium Signaling / physiology
-
Cell Line, Transformed / drug effects
-
Cell Line, Transformed / metabolism
-
Dose-Response Relationship, Drug
-
Endothelin Receptor Antagonists
-
Endothelin-1 / metabolism*
-
Endothelin-1 / pharmacology
-
Fluorescent Dyes
-
Fluorometry
-
Fura-2
-
Ganglia, Spinal / drug effects
-
Ganglia, Spinal / metabolism
-
Intracellular Fluid / drug effects
-
Intracellular Fluid / metabolism*
-
Mice
-
Models, Biological
-
Neuroblastoma
-
Neurons, Afferent / drug effects
-
Neurons, Afferent / metabolism*
-
Nociceptors / drug effects
-
Nociceptors / metabolism*
-
Oligopeptides / pharmacology
-
Pain / chemically induced
-
Pain / metabolism*
-
Pain / physiopathology
-
Peptides, Cyclic / pharmacology
-
Piperidines / pharmacology
-
Rats
-
Receptor, Endothelin A
-
Receptors, Endothelin / agonists
-
Receptors, Endothelin / metabolism*
Substances
-
Antihypertensive Agents
-
Calcium Channels
-
Endothelin Receptor Antagonists
-
Endothelin-1
-
Fluorescent Dyes
-
Oligopeptides
-
Peptides, Cyclic
-
Piperidines
-
Receptor, Endothelin A
-
Receptors, Endothelin
-
BQ 788
-
cyclo(Trp-Asp-Pro-Val-Leu)
-
Calcium
-
Fura-2