Morphological evidence for functional capsaicin receptor expression and calcitonin gene-related peptide exocytosis in isolated peripheral nerve axons of the mouse
Section snippets
Preparations
Outbred CD mice (30–40 g from Charles River, Sulzfeld, Germany) of either sex were killed in a CO2 atmosphere. Sciatic nerves (n=32) were excised from their origin out of the lumbar plexus to the trifurcation into sural, tibial and peroneal nerves and then desheathed under a microscope by removing the epi-perineurium (Sauer et al., 1999). Preparations were wound around acrylic rods, fixed with surgical silk and then washed in carbogen-gassed synthetic interstitial fluid (SIF; 108 mM NaCl,
Capsaicin-induced CGRP release
Stimulation of desheathed nerves with capsaicin at both 3×10−8 M (n=8) and 10−6 M in Ca2+ free SIF (containing 10 mM EGTA; n=4) was ineffective in altering the basal CGRP release. In normal SIF, capsaicin at 3×10−7 (n=8), 10−6 (n=4) and 3×10−6 M (n=8) caused a significant, dose-dependent and reversible increase of CGRP release (5-, 12-, and 14-fold, respectively, Fig. 1).
TRPV1 receptor immunolocalization
TRPV1 immunolocalization was performed in unstimulated nerves where the vast majority of unmyelinated fibers expressed the
Discussion
We present data showing for the first time that the axonal membrane of unmyelinated nerve fibers in the mouse sciatic nerve is able to release CGRP from large vesicles after capsaicin stimulation. The fused vesicles formed the classical exocytotic figures, the omega structures, normally found at the presynaptic membrane of central or peripheral terminals. We have also shown that capsaicin can bind to TRPV1 receptors in the axolemma of peripheral nerves and trigger Ca2+-and
Acknowledgements
The authors would like to thank Mrs. I. Izydorczyk and Mrs. A. Kuhn for their excellent technical assistance. Particular thanks are due to Dr. David Julius (UC San Francisco, USA) for the TRPV1 antibody. This study was supported by the Deutsche Forschungsgemeinschaft SFB 353-B12.
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