Sensitization to heat through G-protein-coupled receptor pathways in the isolated sciatic mouse nerve

Authors

  • Michael J. M. Fischer,

    1. Institut für Physiologie und Pathophysiologie, Universität Erlangen/Nürnberg, Universitätstrasse 17, D-91054 Erlangen, Germany
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  • Peter W. Reeh

    1. Institut für Physiologie und Pathophysiologie, Universität Erlangen/Nürnberg, Universitätstrasse 17, D-91054 Erlangen, Germany
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Dr Michael Fischer, as above.
E-mail: fischer@physiologie1.uni-erlangen.de

Abstract

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 (PGE2) 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.

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