Calcitonin gene-related peptide
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Calcitonin-related polypeptide, beta | |||||||
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Identifiers | |||||||
Symbol | CALCB | ||||||
Alt. symbols | CALC2 | ||||||
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Calcitonin gene-related peptide (CGRP) is a member of the
Function
CGRP is produced in both peripheral and central
CGRP has moderate effects on calcium homeostasis compared to its extensive actions in other areas, such as the autonomic nervous system.
Appetite
As a neuropeptide, CGRP acts as an
Stem cell mobilization
CGRP has a role in human stem cells mobilization. In investigations carried out during last five years, treatment with CGRP resulted in significantly increased CGRP levels in the bone marrow extracellular fluid and substantially increased the number of HSCs mobilized by G-CSF.[11] The results performed on different experiments by the same research group led to the conclusion that G-CSF-induced HSC mobilization is regulated by the nociceptor nerve-derived neuropeptide CGRP. This peptide exerts its effect on HSC mobilization by Ramp 1 pathway.[11]
Receptors
CGRP mediates its effects through a
Regulation
Regulation of the calcitonin gene-related peptide (CGRP) gene is in part controlled by the expression of the
CGRP receptor is found in myelinated A-fibers axon which is required for ligand specificity and function of the receptor. The CGRP receptor has three subunits: receptor activity-modifying protein 1 (RAMP1), calcitonin-like receptor (CLR) and receptor component protein (RCP).[18] The complex central receptor is the G protein-coupled receptor calcitonin receptor-like receptor (CALCRL) which is necessary for CGRP and adrenomedullin (AM receptors). For function CGRP, CALCRL must coincide with RAMP1 where the ligand-binding domain of CGRP is located. It also includes two cytoplasmic proteins that associate with the CALCRL-RAMP1 to form signal transduction. CALCRL contains the Gα subunit, which activates adenylyl cyclase and cAMP-dependent signaling pathways. Receptor-mediated transduction elevates in intracellular cAMP activate protein kinase A, which results in the phosphorylation of multiple targets, including potassium- sensitive ATP channels (KATP channels), extracellular signal-related kinases and transcription factors such as cAMP-responsive element-binding protein (CREB). In smooth muscle of neurovascular region, the elevation of cAMP upon CGRP activation results in vasodilation of the blood vessel. Chronic exposure to CGRP causes degradation of lysosomes.[19]
Research
This section needs to be updated.(February 2018) |
Increased levels of CGRP have been reported in
There is mounting evidence to suggest that CGRP may be beneficial in preventing the development of hypertension and cardiovascular pathologies associated with hypertension.[2] Prophylactic therapy with calcitonin gene‐related peptides (CGRPs) may have unknown fertility consequences for women of child bearing age. This is of particular concern, as females (16.6%) are more genetically predisposed to migraine than are males (7.5%).[27]
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.[28][26] This CGRP then binds to and activates CGRP receptors located around meningeal vessels, causing vasodilation, mast cell degranulation, and plasma extravasation.[13][28][29][30] 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 in plasma drawn from the external jugular vein.[13][28][29][30] Furthermore, intravenous administration of alpha-CGRP is able to induce headache in individuals susceptible to migraine.[31][26]
Medicines
New medicines are now on the market that contain antibodies against either CGRP itself, or its
The first approved by the FDA is called erenumab (trade name Aimovig), produced by pharmaceutical company Amgen and Novartis. It interacts with the CGRP receptor. It is injected once monthly with a dose of 70 or 140 mg. Few adverse effects were reported (most related to injection site reactions) and patients had a significant reduction in migraines.[36][37]
The second approved by the FDA is called fremanezumab (trade name Ajovy), produced by the Teva pharmaceutical company. It interacts with the CGRP protein, whose expression is related to migraine attacks. It may be administered monthly or every three months, giving options for users. Trials have shown a reduction of greater than 50% of migraine days for those who responded. There were few significant side effects during trials, most related to injection site reactions.[38][39]
The third approved by the FDA is called galcanezumab (trade name Emgality), produced by the Eli Lilly Company. It interacts with the CGRP protein, whose expression is related to migraine attacks. It is injected once a month, after the first month having a double dose. The main side effects are injection site reactions.[40][41]
Approved by the FDA in February 2020, ubrogepant (Ubrelvy) is an oral medication manufactured by Allergan.
Also FDA approved in February 2020, eptinezumab (Vyepti), is an intravenous migraine prophylactic medication manufactured by Lundbeck.
The
References
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- ^ a b c d Tepper S. "What to Know About the New CGRP Migraine Treatment Options". American Migraine Foundation. Retrieved 23 February 2019.
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- ^ Bank J (2018-01-16). "CGRP: What You Need To Know". National Headache Foundation. Retrieved 23 February 2019.
- ^ Rosenberg J (18 May 2018). "FDA Approves Erenumab, First CGRP Inhibitor for Prevention of Migraine". AJMC.com. Retrieved 23 February 2019.
- S2CID 67790108.
- ^ "FDA Approves Second Anti-CGRP Treatment for Migraines". American Migraine Foundation. Retrieved 23 February 2019.
- S2CID 52962394.
- ^ "Lilly's Emgality™ (galcanezumab-gnlm) Receives U.S. FDA Approval for the Preventive Treatment of Migraine in Adults". Lilly. Retrieved 23 February 2019.
- S2CID 53107438.
- ^ "Degradants Formed During Phytocannabinoid Processing". www.caymanchem.com. Retrieved 2023-05-10.
- PMID 12040079.
External links
- Calcitonin+Gene-Related+Peptide at the U.S. National Library of Medicine Medical Subject Headings (MeSH)