Title

Nitric oxide regulation of calcitonin gene-related peptide gene expression in rat trigeminal ganglia neurons

Abstract

Calcitonin gene‐related peptide (CGRP) and nitric oxide are involved in the underlying pathophysiology of migraine and other diseases involving neurogenic inflammation. We have tested the hypothesis that nitric oxide might trigger signaling mechanisms within the trigeminal ganglia neurons that would coordinately stimulate CGRP synthesis and release. Treatment of primary trigeminal ganglia cultures with nitric oxide donors caused a greater than four‐fold increase in CGRP release compared with unstimulated cultures. Similarly, CGRP promoter activity was also stimulated by nitric oxide donors and overexpression of inducible nitric oxide synthase (iNOS). Cotreatment with the antimigraine drug sumatriptan greatly repressed nitric oxide stimulation of CGRP promoter activity and secretion. Somewhat surprisingly, the mechanisms of nitric oxide stimulation of CGRP secretion did not require cGMP or PI3‐kinase signaling pathways, but rather, nitric oxide action required extracellular calcium and likely involves T‐type calcium channels. Furthermore, nitric oxide was shown to increase expression of the active forms of the mitogen‐activated protein kinases Jun amino‐terminal kinase and p38 but not extracellular signal‐related kinase in trigeminal neurons. In summary, our results provide new insight into the cellular mechanisms by which nitric oxide induces CGRP synthesis and secretion from trigeminal neurons.

Department(s)

Biology

Document Type

Article

DOI

https://doi.org/10.1111/j.1460-9568.2006.04742.x

Keywords

calcium channels, migraine, mitogen‐activated protein kinase, s sumatriptan

Publication Date

2006

Recommended Citation

Bellamy, Jamie, Elizabeth J. Bowen, Andrew F. Russo, and Paul L. Durham. "Nitric oxide regulation of calcitonin gene‐related peptide gene expression in rat trigeminal ganglia neurons." European Journal of Neuroscience 23, no. 8 (2006): 2057-2066.

Journal Title

European Journal of Neuroscience

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