Journal article
Regulation of Calcitonin Gene-Related Peptide Secretion by a Serotonergic Antimigraine Drug
The Journal of neuroscience, Vol.19(9), pp.3423-3429
05/01/1999
DOI: 10.1523/JNEUROSCI.19-09-03423.1999
PMCID: PMC6782229
PMID: 10212302
Abstract
We have investigated the regulation of calcitonin gene-related peptide (CGRP) release from trigeminal neurons by the serotonergic antimigraine drug sumatriptan. Serum levels of the neuropeptide CGRP are elevated during migraine. Treatment with the drug sumatriptan returns CGRP levels to normal coincident with the alleviation of headache. However, despite this clinical efficacy, the cellular target and mechanism of sumatriptan action are not well understood beyond the pharmacology of its recognition of the 5-HT
1
class of serotonin receptors. We have used cultured trigeminal neurons to demonstrate that sumatriptan can directly repress CGRP secretion from sensory neurons. The stimulated secretion in response to depolarization or inflammatory agents was inhibited, but not the basal secretion rate. Unexpectedly, sumatriptan did not lower cAMP levels, in contrast to the classical role ascribed to the 5-HT
1
receptors. Instead, activation of 5-HT
1
receptors caused a slow and remarkably prolonged increase in intracellular calcium. The inhibition of CGRP secretion is attenuated by the phosphatase inhibitor okadaic acid, suggesting that sumatriptan action is mediated by calcium-recruited phosphatases. These results suggest that 5-HT
1
agonists may block a deleterious feedback loop in migraine at the trigeminal neurons and provide a general mechanism by which this class of drugs can attenuate stimulated neuropeptide release.
Details
- Title: Subtitle
- Regulation of Calcitonin Gene-Related Peptide Secretion by a Serotonergic Antimigraine Drug
- Creators
- Paul L DurhamAndrew F Russo
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.19(9), pp.3423-3429
- DOI
- 10.1523/JNEUROSCI.19-09-03423.1999
- PMID
- 10212302
- PMCID
- PMC6782229
- NLM abbreviation
- J Neurosci
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Publisher
- Society for Neuroscience
- Language
- English
- Date published
- 05/01/1999
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center
- Record Identifier
- 9984020862402771
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