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calcitonin-related polypeptide, beta
Identifiers
Symbol CALCB
Alt. symbols CALC2
Entrez 797
HUGO 1438
OMIM 114160
RefSeq NM_000728
UniProt P10092
Other data
Locus Chr. 11 p14.2-p12

Calcitonin gene related peptide (CGRP) is a member of the calcitonin family of peptides, which in humans exists in two forms, α-CGRP and β-CGRP. α-CGRP is a 37 amino acid peptide and is formed from the alternative splicing of the calcitonin/CGRP gene located on chromosome 11. CGRP is one of the most abundant peptides produced in both peripheral and central neurons. [1] It is the most potent peptide vasodilator and can function in the transmission of pain[2][3]. In the trigeminal vascular system the cell bodies on the [trigeminal ganglion] are the main source of CGRP. CGRP is thought to play a role in cardiovascular homeostasis and nociception. CGRP mediates its effects though a heteromeric receptor composed of a G protein-coupled receptor called calcitonin receptor-like receptor (CLR) and a receptor activity-modifying protein (RAMP1) [4]. CGRP receptors are found throughout the body suggesting that the protein may modulate a variety of physiological functions in all major systems (eg, respiratory , endocrine , gastrointestinal, immune, and cardiovascular) [5]. Increased levels of CGRP have been reported in migraine and Temporomandibular joint disorder patients as well as a variety of other diseases such as cardiac failure, hypertension, and sepsis [6][7][8][9][10][11]

Regulation of the calcitonin gene related peptide (CGRP) gene is in part controlled by the expression of the mitogen-activated protein kinases (MAPK) signaling pathway[12],cytokines such as TNFα [13] and iNOS [14] . 5HT1 agonists such as sumatriptan increase intracellular calcium which cause decreases in CGRP promoter activity[12]. Botulinum toxin type A is able to prevent stimulated release of CGRP through the cleavage of SNAP-25 protein[15]. Receptor antagonists such as telcagepant, which is in phase III from Merck Pharmaceuticals, also has promise in limiting the effects of CGRP [16].

The Role of CGRP in headache

Preclinical evidence suggests that during a migraine, activated primary sensory neurons (meningeal nociceptors) in the trigeminal ganglion release CGRP from their peripherally projecting nerve endings located within the meninges.[17] This CGRP then binds to and activates CGRP receptors located around meningeal vessels causing vasodilation, mast cell degranulation and plasma extravasation.[5][17][18][19] Human observations have further implicated the role of CGRP in the pathophysiology of migraine. Activation of primary sensory neurons in the trigeminal vascular system in humans can cause the release of CGRP. During some migraine attacks increased concentrations of CGRP can be found in both saliva and plasma drawn from the external jugular vein.[5][17][18][19] Furthermore intravenous administration of alpha-CGRP is able to induce headache in individuals susceptible to migraine.[20]

External links

References

  1. ^ Rosenfeld, M., et al. (1983). "Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing". Nature 304 (5922): 129–135. doi:10.1038/304129a0. PMID 6346105. 
  2. ^ Brain SD, Williams TJ, Tippins JR, Morris HR, MacIntyre I (1985). "Calcitonin gene-related peptide is a potent vasodilator". Nature 313 (5997): 54–6. doi:10.1038/313054a0. PMID 3917554. 
  3. ^ McCulloch, J., et al. (1986). "Calcitonin gene-related peptide: Functional role in cerebrovascular regulation". Proc Natl Acad Sci USA 83: 5731–5735. doi:10.1073/pnas.83.15.5731. PMID 3488550. 
  4. ^ Poyner, D., et al. (2002). "International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors.". Pharmacol Rev 54 (2): 233–246. doi:10.1124/pr.54.2.233. PMID 12037140. 
  5. ^ a b c Arulmani, U., et al. (2004). "Calcitonin gene-related peptide and its role in migraine pathophysiology". Eur J Pharmacol 500: 315–30. doi:10.1016/j.ejphar.2004.07.035. PMID 15464043. 
  6. ^ Buzzi, M., M. Bonamini, and M. Moskowitz (1995). "Neurogenic model of migraine". Cephalgia 15 (4): 277–280. doi:10.1046/j.1468-2982.1995.1504277.x. PMID 7585923. 
  7. ^ Goto, K., et al. (1992). "Calcitonin gene-related peptide in the regulation of cardiac function". Ann NY Acad Sci 267: 194–203. doi:10.1111/j.1749-6632.1992.tb22768.x. PMID 1637085. 
  8. ^ Joyce, C., et al. (1990). "Calcitonin gene-related peptide levels are elevated in patients with sepsis". Surgery 108 (6): 1097–101. PMID 2247835. 
  9. ^ Edvinsson, L. and P. Goadsby (1994). "Neuropeptides in migraine and cluster headache". Cephalalgia 14 (5): 320–7. doi:10.1046/j.1468-2982.1994.1405320.x. PMID 7828188. 
  10. ^ Ferrari, M. and P. Saxena (1993). "On serotonin and migraine: a clinical and pharmacological review". Cephalalgia 13 (3): 151–65. doi:10.1046/j.1468-2982.1993.1303151.x. PMID 8395342. 
  11. ^ Goadsby, P. and L. Edvinsson (1993). "Human in vivo evidence for trigeminovascular activation in cluster headache. Neuropeptide changes and effects of acute attacks therapies". Brain 117: 427–34. doi:10.1093/brain/117.3.427. PMID 7518321. 
  12. ^ a b Durham, P. and A. Russo (2003). "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 23 (3): 807–815. PMID 12574409. 
  13. ^ Schafers, M., et al. (2003). "Tumor necrosis factor-alpha induces mechanical allodynia after spinal nerve ligation by activation of p38 MAPK in primary sensory neurons". J Neurosci 23 (7): 2517–21. PMID 12684435. 
  14. ^ Li, J., C. Vause, and P. Durham (2008). "Calcitonin gene-related peptide stimulation of nitric oxide synthesis and release from trigeminal ganglion glial cells". Brain Research 1196: 22–32. doi:10.1016/j.brainres.2007.12.028. PMID 18221935. 
  15. ^ Durham, P., R. Cady, and R. Cady (2004). "Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: implications for migraine therapy". Headache 44 (1): 35–42. doi:10.1111/j.1526-4610.2004.04007.x. PMID 14979881. 
  16. ^ Tepper, S.J. and M.J. Stillman (2008). "Clinical and preclinical rationale for CGRP-receptor antagonists in the treatment of migraine". Headache 48 (8): 1259–68. doi:10.1111/j.1526-4610.2008.01214.x. PMID 18808506. 
  17. ^ a b c Durham, P (2006). "Calcitonin gene-related peptide (CGRP) and migraine". Headache 48: S3–8. doi:10.1111/j.1526-4610.2006.00483.x. PMID 16927957. 
  18. ^ a b Goadsby, P., L. Edvinsson, and R. Elkman (1990). "Vasoactive peptide release in the extracerebral circulation of humans during migraine headache". Ann Neurol 28 (2): 183–7. doi:10.1002/ana.410280213. PMID 1699472. 
  19. ^ a b Edvinsson, L. (2006). "Neuronal signal substances as biomarkers of migraine". Headache 46 (7): 1088–94. doi:10.1111/j.1526-4610.2006.00502.x. PMID 16866713. 
  20. ^ Lassen, L., et al. (2002). "CGRP may play a causative role in migraine". Cephalalgia 22 (1): 54–61. doi:10.1046/j.1468-2982.2002.00310.x. PMID 11993614. 
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