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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\u2010fold 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\u2010kinase signaling pathways, but rather, nitric oxide action required extracellular calcium and likely involves T\u2010type calcium channels. Furthermore, nitric oxide was shown to increase expression of the active forms of the mitogen\u2010activated protein kinases Jun amino\u2010terminal kinase and p38 but not extracellular signal\u2010related 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.<\/jats:p>","DOI":"10.1111\/j.1460-9568.2006.04742.x","type":"journal-article","created":{"date-parts":[[2006,4,21]],"date-time":"2006-04-21T11:39:35Z","timestamp":1145619575000},"page":"2057-2066","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":128,"title":["Nitric oxide regulation of calcitonin gene\u2010related peptide gene expression in rat trigeminal ganglia neurons"],"prefix":"10.1111","volume":"23","author":[{"given":"Jamie","family":"Bellamy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Bowen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew F.","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul L.","family":"Durham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,4,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1526-4610.2001.111006084.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0202-136"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"8036","DOI":"10.1016\/S0021-9258(19)57508-1","article-title":"Cyclic AMP and phorbol esters separately induce growth inhibition, calcitonin secretion, and calcitonin gene transcription in cultured human medullary thyroid carcinoma","volume":"261","author":"De Bustros A.","year":"1986","journal-title":"J. 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