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have or establish a relationship to; "She relates well to her peers"
be in a relationship with; "How are these two observations related?" (同)interrelate
give an account of; "The witness related the events"
connected by kinship, common origin, or marriage
being connected either logically or causally or by shared characteristics ; "painting and the related arts"; "school-related activities"; "related to micelle formation is the...ability of detergent actives to congregate at oil-water interfaces" (同)related to
(genetics) a segment of DNA that is involved in producing a polypeptide chain; it can include regions preceding and following the coding DNA as well as introns between the exons; it is considered a unit of heredity; "genes were formerly called factors" (同)cistron, factor
thyroid hormone that tends to lower the level of calcium in the blood plasma and inhibit resorption of bone (同)thyrocalcitonin
amide combining the amino group of one amino acid with the carboxyl group of another; usually obtained by partial hydrolysis of protein

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/01/06 20:23:49」(JST)

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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. The less-studied β-CGRP differs in three amino acids (in humans) and is encoded in a separate gene in the same vicinity.^[1]

Function

CGRP is produced in both peripheral and central neurons.^[2] It is a potent peptide vasodilator and can function in the transmission of pain.^[3]^[4] In the spinal cord, the function and expression of CGRP may differ depending on the location of synthesis. CGRP is derived mainly from the cell bodies of motor neurons when synthesized in the ventral horn of the spinal cord and may contribute to the regeneration of nervous tissue after injury. Conversely, CGRP is derived from dorsal root ganglion when synthesized in the dorsal horn of the spinal cord and may be linked to the transmission of pain.^[5] 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.

Receptors

CGRP mediates its effects though a heteromeric receptor composed of a G protein-coupled receptor called calcitonin receptor-like receptor (CALCRL) and a receptor activity-modifying protein (RAMP1).^[6] CGRP receptors are found throughout the body, suggesting that the protein may modulate a variety of physiological functions in all major systems (e.g., respiratory, endocrine, gastrointestinal, immune, and cardiovascular).^[7]

Regulation

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,^[8] cytokines such as TNFα ^[9] and iNOS.^[10]

5HT1 receptor agonists, such as sumatriptan, increase intracellular calcium, which cause decreases in CGRP promoter activity.^[8] Botulinum toxin type A is able to prevent stimulated release of CGRP through the cleavage of SNAP-25 protein.^[11] Receptor antagonists may also have the potential of limiting the effects of CGRP, though one promising drug candidate in this class (telcagepant) was withdrawn^[12] by Merck Pharmaceuticals after phase III trials.^[13]

Clinical significance

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.^[14]^[15]^[16]^[17]^[18]^[19]

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.^[20] This CGRP then binds to and activates CGRP receptors located around meningeal vessels, causing vasodilation, mast cell degranulation, and plasma extravasation.^[7]^[20]^[21]^[22] 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.^[7]^[20]^[21]^[22] Furthermore intravenous administration of alpha-CGRP is able to induce headache in individuals susceptible to migraine.^[23]

The source of CGRP in migraine (and other pain conditions) is largely thought to derive from the peptidergic peripheral innervation where alpha-CGRP is the predominant isoform produced by sensory neurons. It is the alpha-CGRP isoform that is presumed to be the primary contributor to pain mechanisms. However, more recent evidence demonstrates that CGRP is expressed among keratinocytes of the epidermis where it is predominantly the beta form.^[24] Furthermore, CGRP expression in keratinocytes is substantially increased in certain human chronic pain conditions and animal models of induced chronic pain conditions, whereas the alpha-CGRP containing peptidergic innervation is decreased in painful skin sites.^[24] Therefore, keratinocyte-derived beta-CGRP may have an important role in chronic pain mechanisms, as well as other dermatologic disorders known to involve changes in CGRP levels, such as psoriasis. Although very little is known about the functional differences between these two isoforms, research has demonstrated that the beta-CGRP is also expressed among enteric neurons of the gut, and CGRP has been implicated in mechanisms of visceral pain disorders, such as irritable bowel syndrome.

References

^ Rezaelan, A.H., et al. (2009). "AlphaCGRP and betaCGRP transcript amount in mouse tissues of various developmental stages and their tissue expression sites". Brain and Development 31 (9): 682–693. doi:10.1016/j.braindev.2008.10.011. PMID 19062206.
^ 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.
^ 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.
^ McCulloch, J., et al. (1986). "Calcitonin gene-related peptide: functional role in cerebrovascular regulation". Proc Natl Acad Sci USA 83 (15): 5731–5735. doi:10.1073/pnas.83.15.5731. PMC 386363. PMID 3488550. //www.ncbi.nlm.nih.gov/pmc/articles/PMC386363/.
^ Chen LJ, Zhang FG, Li J, et al. (January 2010). "Expression of calcitonin gene-related peptide in ventral and dorosal horns of the spinal cord after brachial plexus injury". J Clin Neurosci 17 (1): 87–91. doi:10.1016/j.jocn.2009.03.042. PMID 19969463.
^ 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.
^ ^a ^b ^c Arulmani, U., et al. (2004). "Calcitonin gene-related peptide and its role in migraine pathophysiology". Eur J Pharmacol 500 (1–3): 315–30. doi:10.1016/j.ejphar.2004.07.035. PMID 15464043.
^ ^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.
^ 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.
^ 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. PMC 2268710. PMID 18221935. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2268710/.
^ 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.
^ Merck Announces Second Quarter 2011 Financial Results
^ 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.
^ 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.
^ 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.
^ Joyce, C., et al. (1990). "Calcitonin gene-related peptide levels are elevated in patients with sepsis". Surgery 108 (6): 1097–101. PMID 2247835.
^ 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.
^ 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.
^ 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 (3): 427–34. doi:10.1093/brain/117.3.427. PMID 7518321.
^ ^a ^b ^c Durham, P (2006). "Calcitonin Gene-Related Peptide (CGRP) and Migraine". Headache 48 (Suppl 1): S3–8. doi:10.1111/j.1526-4610.2006.00483.x. PMC 3134175. PMID 16927957. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3134175/.
^ ^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.
^ ^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.
^ 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.
^ ^a ^b Hou Q, Barr T, Gee L, Vickers J, Wymer J, Borsani E, Rodella L, Getsios S, Burdo T, Eisenberg E, Guha U, Lavker R, Kessler J, Chittur S, Fiorino D, Rice F, Albrecht P (June 2011). "Keratinocyte Expression of CGRPβ: Implications for Neuropathic and Inflammatory Pain Mechanisms". Pain 152 (9): 2036–51. doi:10.1016/j.pain.2011.04.033. PMC 3157543. PMID 21641113. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3157543/.

External links

Calcitonin+Gene-Related+Peptide at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 成人における片頭痛の病態生理、臨床症状、および診断 pathophysiology clinical manifestations and diagnosis of migraine in adults
2. 成人における片頭痛の急性期治療 acute treatment of migraine in adults
3. 小児における片頭痛の病態生理、臨床的特徴、および診断 pathophysiology clinical features and diagnosis of migraine in children
4. レイノー現象の病因 pathogenesis of the raynaud phenomenon
5. 気道の神経制御 neuronal control of the airways

English Journal

Immunocytochemical organization and sour taste activation in the rostral nucleus of the solitary tract of mice.

Stratford JM1, Thompson JA2, Finger TE1,3.
The Journal of comparative neurology.J Comp Neurol.2017 Feb 1;525(2):271-290. doi: 10.1002/cne.24059. Epub 2016 Aug 11.
Sensory inputs from the oropharynx terminate in both the trigeminal brainstem complex and the rostral part of the nucleus of the solitary tract (nTS). Taste information is conveyed via the facial and glossopharyngeal nerves, while general mucosal innervation is carried by the trigeminal and glossoph
PMID 27292295

Increased expression of nerve growth factor correlates with visceral hypersensitivity and impaired gut barrier function in diarrhoea-predominant irritable bowel syndrome: a preliminary explorative study.

Xu XJ1,2, Zhang YL2, Liu L3, Pan L4, Yao SK1,2.
Alimentary pharmacology & therapeutics.Aliment Pharmacol Ther.2017 Jan;45(1):100-114. doi: 10.1111/apt.13848. Epub 2016 Nov 9.
BACKGROUND: Neural-immune-endocrine network mechanism has attracted increased attention in diarrhoea-predominant irritable bowel syndrome (IBS-D). Pre-clinical evidence indicates that nerve growth factor (NGF) mediates visceral hypersensitivity and gut barrier dysfunction, via interactions with mast
PMID 27862119

Effect of lentiviral vector overexpression α-calcitonin gene-related peptide on titanium implant osseointegration in α-CGRP-deficient mice.

Xiang L1, Ma L1, Wei N1, Wang T1, Yao Q1, Yang B1, Xiong Y1, Wu Y1, Gong P2.
Bone.Bone.2017 Jan;94:135-140. doi: 10.1016/j.bone.2015.08.009. Epub 2015 Aug 8.
α-Calcitonin gene-related peptide (α-CGRP) plays a significant pathophysiological role in bone development, metabolism and remodeling around dental implants. However, the half-life of α-CGRP in plasma is only 10min, which affects its long-time application and an alternative approach should be dev
PMID 26265538

Japanese Journal

Current Perspective : The Mechanism of Calcitonin Gene-Related Peptide-Containing Nerve Innervation

Hashikawa-Hobara Narumi,Hashikawa Naoya,Zamami Yoshito [他]
Journal of pharmacological sciences 119(2), 117-121, 2012-06
NAID 40019310125

Cloning of two members of the calcitonin-family receptors from stingray, Dasyatis akajei: Possible physiological roles of the calcitonin family in osmoregulation

Suzuki Nobuo,Sekiguchi Toshio,Satake Honoo,Kato Kanoko,Nishiyama Yudai,Takahashi Hideya,Dankse Janine A.,Martin T. John,Hattori Atsuhiko,Nakano Masaki,Kakikawa Makiko,Yamada Sotoshi,Ogoshi Maho,Hyodo Susumu,Yamaguchi Yoko,Chowdhur Vishwajit S.,Hayakawa Kazuichi,Funahashi Hisayuki,Sakamoto Tatsuya,Sasayama Yuichi
Gene
… In cartilaginous fish, two cDNAs encoding calcitonin-family receptors were isolated for the first time from the stingray brain. … The amino acid identity of this receptor to human calcitonin-receptor-like receptor (CRLR) is 64.5%, frog CRLR is 64.7%, and flounder CRLR is 61.2% and this was higher than to human calcitonin receptor (CTR) (46.1%), frog CTR (54.7%), and flounder CTR (48.9%). …
NAID 120004140850

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★リンクテーブル★

リンク元	「CGRP」「カルシトニン遺伝子関連ペプチド」
拡張検索	「calcitonin gene-related peptide receptor」
関連記事	「relate」

「CGRP」

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-related polypeptide alpha
Identifiers
Symbol	CALCA
Alt. symbols	CALC1
Entrez	796
HUGO	1437
OMIM	114130
RefSeq	NM_001741
UniProt	P06881
Other data
Locus	Chr. 11 p15.2