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Sensitization to heat through G‐protein‐coupled receptor pathways in the isolated sciatic mouse nerve
Author(s) -
Fischer Michael J. M.,
Reeh Peter W.
Publication year - 2007
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2007.05582.x
Subject(s) - calcitonin gene related peptide , trpv1 , chemistry , protein kinase c , sciatic nerve , endocrinology , medicine , receptor , sensory neuron , bradykinin , microbiology and biotechnology , stimulation , protein kinase a , signal transduction , transient receptor potential channel , kinase , biology , biochemistry , neuropeptide
We have previously shown that isolated rat sciatic nerve axons express capsaicin, heat and proton sensitivity and respond to stimulation with a Ca ++ ‐dependent and graded calcitonin gene related peptide (CGRP) release. There is morphological evidence for stimulated vesicular exocytosis and for capsaicin receptor, transient receptor potential vanilloid type‐1 (TRPV1, formerly VR1) translocation in the axolemma of unmyelinated nerve fibres. In sensory nerve terminals CGRP release in response to noxious heat can be sensitized by activation of G‐protein‐coupled receptors and related protein kinases. We present evidence that also in isolated mouse sciatic nerve axons the intracellular protein kinase A (PKA)‐ and C (PKC)‐dependent transduction pathways modulate heat‐induced (45 °C) CGRP release. This is demonstrated using the direct activators, forskolin and phorbol 12‐myristate 13‐acetate (PMA), as well as prostaglandin E2 (PGE 2 ) and bradykinin acting through G‐protein‐coupled receptors. Inhibition at rest of protein kinases A or C left heat‐induced CGRP release unchanged. In TRPV1 knockout animals no sensitization to heat was observed using a combined stimulation by prostaglandin E2 and bradykinin. To a surprising degree, peripheral nerve axons resemble peripheral sensory terminals in their common properties of sensory and signal transduction.