The effects of calcitonin gene-related peptide (CGRP) in the body include:
- Blood vessels:
- Pain perception:
- CGRP mediates pain perception and has been proposed to contribute to pain transmission and inflammation.
- CGRP modulates the immune system and binds to certain receptors on the immune cells, thereby reducing their action.
- Action on the bone:
- CGRP helps in bone formation and restoration. Studies have reported that it may play important role in bone growth and metabolism.
- Action on the gastrointestinal system:
- CGRP increases gastrointestinal motility by aiding in peristalsis.
- Biological effects of CGRP on the gastrointestinal system include an increase in the intestinal blood flow and relaxation of the smooth muscles in the gut.
What is CGRP?
Calcitonin gene-related peptide (CGRP) is a neuropeptide, which is a type of protein that acts as a signaling molecule in the brain.
CGRP is a chemical messenger made up of small chains of amino acids that are synthesized and released by neurons or nerve fibers. The function of the neurons is to convey messages or commands from the brain to the various tissues of the body.
How is CGRP produced in our body?
Calcitonin gene-related peptide (CGRP) is produced from the cell body of the nerve cells or neurons.
When the nerves are activated, CGRP and other neuropeptides are released that promote the release of inflammatory mediators, leading to pain, swelling, and other signs of inflammation.
CRPG levels increase in conditions such as:
What is the role of CGRP in migraines?
Calcitonin gene-related peptide (CGRP) levels increase during acute migraines. Triptans, which are normally used during migraine attacks, primarily reduce the CGRP level. This decrease corresponds with migraine relief.
Treatment with a CGRP receptor antagonist relieves migraines through the following possible mechanisms:
- Blocking neurogenic inflammation: Binding of CGRP receptor antagonists to CGRP receptors located on the mast cells (types of cells involved in inflammation) inhibits inflammation caused by the trigeminal nerve release of CGRP onto the mast cells within the meninges (membrane layers covering the brain).
- Decreasing artery dilation: By blocking CGRP receptors located in the smooth muscle cells within vessel walls, CGRP receptor antagonists inhibit the pathologic dilation of intracranial arteries.
- Inhibiting pain transmission: The binding of CGRP receptor antagonists to CGRP receptors suppresses the transmission of pain by inhibiting the central relay of pain signals from the trigeminal nerve to pain centers in the brain.
What are CGRP antagonists?
When released in excess, calcitonin gene-related peptide (CGRP) causes intense inflammation in coverings of the brain (meninges). The mechanism of action of CGRP antagonists is by blocking CGRP receptors of the nerve cells, which trigger intense pain and activate the CGRP cascade. CGRP antagonists bind to CGRP receptors and do not allow the binding of CGRP to its receptor.
Some CGRP antagonists include:
- Anti-CGRP monoclonal antibodies: These drugs bind to CGRP receptors or CGRP itself, and include:
- Gepants: These drugs are small molecules that bind to and block the CGRP receptor, without causing any vasoconstrictive effect, and include:
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