Activation of Excitatory Amino Acid Receptors in Bovine Dental Pulp Evokes the Release of iCGRP

Abstract

The activation of excitatory amino acid (EAA) receptors within the central nervous system is associated with numerous centrally mediated phenomena, including hyperalgesia. However, relatively little is known about the peripheral mechanisms which these receptors may regulate when activated. This research evaluated the hypothesis that EAA receptors in bovine dental pulp activate a population of peptidergic sensory neurons as measured by the release of immunoreactive calcitonin gene-related peptide (iCGRP), a neuropeptide associated with neurogenic inflammation. In vitro superfusion of bovine dental pulp was used to evaluate the regulation of iCGRP secretion by the EAA receptor agonists AMPA, kainate, NMDA, and L-glutamate. Both AMPA and kainate stimulated the release of iCGRP in a concentration-dependent manner (AMPA EC₅₀ = 0.27 ± 3.3 nM; kainate EC₅₀ = 3.2 ± 1.1 μM). Pre-treatment and coadministration of the AMPA/kainate receptor antagonist CNQX significantly reduced the iCGRP release evoked by either of these agonists. In contrast, neither NMDA nor L-glutamate induced any consistent changes in iCGRP release. These results suggest that the activation of AMPA and kainate receptors in dental pulp may contribute to peripheral release of vasoactive neuropeptides which mediate a neurogenic component of inflammation.