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Effect of Carbon Dioxide on Calcitonin Gene‐Related Peptide Secretion From Trigeminal Neurons
Author(s) -
Vause Carrie,
Bowen Elizabeth,
Spierings Egilius,
Durham Paul
Publication year - 2007
Publication title -
headache: the journal of head and face pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.14
H-Index - 119
eISSN - 1526-4610
pISSN - 0017-8748
DOI - 10.1111/j.1526-4610.2007.00850.x
Subject(s) - calcitonin gene related peptide , capsaicin , nitric oxide , trigeminal ganglion , calcitonin , chemistry , medicine , endocrinology , neuropeptide , biochemistry , biology , neuroscience , sensory system , receptor
Objective.— The goal of this study was to determine whether the physiological effects of carbon dioxide (CO 2 ) involve regulation of CGRP secretion from trigeminal sensory neurons. Background.— The neuropeptide calcitonin gene‐related peptide (CGRP) is implicated in the pathophysiology of allergic rhinosinusitis and migraine. Recent clinical evidence supports the use of noninhaled intranasal delivery of 100% CO 2 for treatment of these diseases. Patients report 2 distinct physiological events: first, a short duration stinging or burning sensation within the nasal mucosa, and second, alleviation of primary symptoms. Methods.— Primary cultures of rat trigeminal ganglia were utilized to investigate the effects of CO 2 on CGRP release stimulated by a depolarizing stimulus (KCl), capsaicin, nitric oxide, and/or protons. The amount of CGRP secreted into the culture media was determined using a CGRP‐specific radioimmunoassay. Intracellular pH and calcium levels were measured in cultured trigeminal neurons in response to CO 2 and stimulatory agents using fluorescent imaging techniques. Results.— Incubation of primary trigeminal ganglia cultures at pH 6.0 or 5.5 was shown to significantly stimulate CGRP release. Similarly, CO 2 treatment of cultures caused a time‐dependent acidification of the media, achieving pH values of 5.5‐6 that stimulated CGRP secretion. In addition, KCl, capsaicin, and a nitric oxide donor also caused a significant increase in CGRP release. Interestingly, CO 2 treatment of cultures under isohydric conditions, which prevents extracellular acidification while allowing changes in PCO 2 values, significantly repressed the stimulatory effects of KCl, capsaicin, and nitric oxide on CGRP secretion. We found that CO 2 treatment under isohydric conditions resulted in a decrease in intracellular pH and inhibition of the KCl‐ and capsaicin‐mediated increases in intracellular calcium. Conclusions.— Results from this study provide the first evidence of a unique regulatory mechanism by which CO 2 inhibits sensory nerve activation, and subsequent neuropeptide release. Furthermore, the observed inhibitory effect of CO 2 on CGRP secretion likely involves modulation of calcium channel activity and changes in intracellular pH.