An Evaluation of NMDA and Metabotropic Glutamate Receptor Modulation of Capsaicin-Evoked iCGRP Release from Bovine Dental Pulp
The general focus of this research is the pharmacological regulation of a specific population of sensory nerurons in dental pulp that contain and release calcitonin gene related perptide (CGRP). The release of CGRP from the peripheral terminals of these nerves is responsible for the neurogenic component of inflammation. The hypothesis tested in this project is that one class of excitatory amino acid receptor, specifically, the metabotropic glutamate receptors (mGluRs), modify the release of CGRP produced by capsaicin. Capsaicin, the pungent ingredient in hot chilli peppers, selectively activates a population of sensory neruons that contain and release CGRP. This project will incorporate the method of in vitro bovine dental pulp superfusion to evaluate the pharmacological mechanisms responsible for the mGluR modulation of capsaicin-evoked CGRP release from dental pulp. Drugs that selectively bind to the mGluRs will be administered to the pulp tissue and changes in the subsequent release of CGRP will be measured by radioimmunoassay. Additional experiments to be evaluated include the anatomical localization of the mGluRs in bovine dental pulp by immunohistochemistry and the endogenous sources of excitatory amino acids that bind to the mGluRs by HPLC.
