Noxious heat-induced CGRP release from rat sciatic nerve axons in vitro

Noxious heat may act as an endogenous activator of the ionotropic capsaicin receptor (VR1) and of its recently found homologue VRL1, expressed in rat dorsal root ganglion cells and present along their nerve fibres. We have previously reported that capsaicin induces receptor‐mediated and Ca++‐depende...

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Bibliographic Details
Published in:The European journal of neuroscience 2001-10, Vol.14 (8), p.1203-1208
Main Authors: Sauer, S. K., Reeh, P. W., Bove, G. M.
Format: Article
Language:English
Subjects:
Animals
Axons - metabolism
Calcitonin Gene-Related Peptide - metabolism
calcium dependency
capsaicin
Capsaicin - agonists
Capsaicin - analogs & derivatives
Capsaicin - pharmacology
capsazepine
Coloring Agents - pharmacology
Dose-Response Relationship, Drug
Ganglia, Spinal - metabolism
Ganglia, Spinal - physiopathology
Hot Temperature - adverse effects
Male
Nociceptors - metabolism
Pain - metabolism
Pain - physiopathology
Potassium - pharmacology
Rats
Rats, Wistar
Receptors, Drug - agonists
Receptors, Drug - antagonists & inhibitors
Receptors, Drug - metabolism
Ruthenium Red
Ruthenium Red - pharmacology
Sciatic Nerve - metabolism
Sciatic Nerve - physiopathology
vanilloid receptor
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Summary:Noxious heat may act as an endogenous activator of the ionotropic capsaicin receptor (VR1) and of its recently found homologue VRL1, expressed in rat dorsal root ganglion cells and present along their nerve fibres. We have previously reported that capsaicin induces receptor‐mediated and Ca++‐dependent calcitonin gene‐related peptide (CGRP) release from axons of the isolated rat sciatic nerve. Here we extended the investigation to noxious heat stimulation and the transduction mechanisms involved. Heat stimulation augmented the CGRP release from desheathed sciatic nerves in a log–linear manner with a Q10 of ≈ 15 and a threshold between 40 and 42 °C. The increases were 1.75‐fold at 42 °C, 3.8‐fold at 45 °C and 29.1‐fold at 52 °C; in Ca++‐free solution these heat responses were abolished or reduced by 71 and 92%, respectively. Capsazepine (10 µm) and Ruthenium Red (1 µm) used as capsaicin receptor/channel antagonists did not significantly inhibit the heat‐induced release. Pretreatment of the nerves with capsaicin (100 µm for 30 min) caused complete desensitization to 1 µm capsaicin, but a significant heat response remained, indicating that heat sensitivity is not restricted to capsaicin‐sensitive fibres. The sciatic nerve axons responded to heat, potassium and capsaicin stimulation with a Ca++‐dependent CGRP release. Blockade of the capsaicin receptor/channels had little effect on the heat‐induced neuropeptide release. We conclude therefore that other heat‐activated ion channels than VR1 and VRL1 in capsaicin‐sensitive and ‐insensitive nerve fibres may cause excitation, axonal Ca++ influx and subsequent CGRP release.
ISSN:0953-816X
1460-9568
DOI:10.1046/j.0953-816x.2001.01741.x