QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (59) Citing Articles via Google Scholar Google Scholar Articles by Durham, P. L. Articles by Russo, A. F. Search for Related Content PubMed PubMed Citation Articles by Durham, P. L. Articles by Russo, A. F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB POTASSIUM CHLORIDE

 Previous Article  |  Next Article 

The Journal of Neuroscience, May 1, 1999, 19(9):3423-3429

Regulation of Calcitonin Gene-Related Peptide Secretion by a Serotonergic Antimigraine Drug

Paul L. Durham and Andrew F. Russo

Department of Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242

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-HT₁ 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-HT₁ receptors. Instead, activation of 5-HT₁ 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-HT₁ 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.

Key words: CGRP; serotonin receptors; trigeminal neurons; calcium; phosphatase; migraine; neuropeptide

---

Copyright © 1999 Society for Neuroscience  0270-6474/99/1993423-07$05.00/0

This article has been cited by other articles:

				J. Meng, J. Wang, G. Lawrence, and J. O. Dolly Synaptobrevin I mediates exocytosis of CGRP from sensory neurons and inhibition by botulinum toxins reflects their anti-nociceptive potential J. Cell Sci., August 15, 2007; 120(16): 2864 - 2874. [Abstract] [Full Text] [PDF]

				Z. Zhang, C. S. Winborn, B. Marquez de Prado, and A. F. Russo Sensitization of Calcitonin Gene-Related Peptide Receptors by Receptor Activity-Modifying Protein-1 in the Trigeminal Ganglion J. Neurosci., March 7, 2007; 27(10): 2693 - 2703. [Abstract] [Full Text] [PDF]

				E. Fabbretti, M. D'Arco, A. Fabbro, M. Simonetti, A. Nistri, and R. Giniatullin Delayed upregulation of ATP P2X3 receptors of trigeminal sensory neurons by calcitonin gene-related peptide. J. Neurosci., June 7, 2006; 26(23): 6163 - 6171. [Abstract] [Full Text] [PDF]

				A. M. Strassman and D. Levy Response Properties of Dural Nociceptors in Relation to Headache J Neurophysiol, March 1, 2006; 95(3): 1298 - 1306. [Abstract] [Full Text] [PDF]

				P. L. Durham and A. F. Russo Stimulation of the Calcitonin Gene-Related Peptide Enhancer by Mitogen-Activated Protein Kinases and Repression by an Antimigraine Drug in Trigeminal Ganglia Neurons J. Neurosci., February 1, 2003; 23(3): 807 - 815. [Abstract] [Full Text] [PDF]

				A. Bhattacharya, K. W. Schenck, and M. L. Cohen Amplification of sumatriptan-induced contraction in rabbit saphenous vein but not in basilar artery Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H719 - H726. [Abstract] [Full Text] [PDF]

				S. Mora, P. L. Durham, J. R. Smith, A. F. Russo, A. Jeromin, and J. E. Pessin NCS-1 Inhibits Insulin-stimulated GLUT4 Translocation in 3T3L1 Adipocytes through a Phosphatidylinositol 4-Kinase-dependent Pathway J. Biol. Chem., July 19, 2002; 277(30): 27494 - 27500. [Abstract] [Full Text] [PDF]

				S. J. Tepper, A. M. Rapoport, and F. D. Sheftell Mechanisms of Action of the 5-HT1B/1D Receptor Agonists Arch Neurol, July 1, 2002; 59(7): 1084 - 1088. [Abstract] [Full Text] [PDF]

				D. Paul, D. Yao, P. Zhu, L. D. Minor, and M. M. Garcia 5-Hydroxytryptamine3 (5-HT3) Receptors Mediate Spinal 5-HT Antinociception: An Antisense Approach J. Pharmacol. Exp. Ther., August 1, 2001; 298(2): 674 - 678. [Abstract] [Full Text] [PDF]

				A. M. Carruthers, L. A. Sellers, D. W. Jenkins, E. M. Jarvie, W. Feniuk, and P. P. A. Humphrey Adenosine A1 Receptor-Mediated Inhibition of Protein Kinase A-Induced Calcitonin Gene-Related Peptide Release from Rat Trigeminal Neurons Mol. Pharmacol., June 1, 2001; 59(6): 1533 - 1541. [Abstract] [Full Text]

				P. L. Durham and A. F. Russo Differential Regulation of Mitogen-Activated Protein Kinase-Responsive Genes by the Duration of a Calcium Signal Mol. Endocrinol., October 1, 2000; 14(10): 1570 - 1582. [Abstract] [Full Text]

				J. L. Wood and A. F. Russo Autoregulation of Cell-specific MAP Kinase Control of the Tryptophan Hydroxylase Promoter J. Biol. Chem., June 8, 2001; 276(24): 21262 - 21271. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help