Calcitonin gene-related peptide

Human calcitonin bound to receptor PDB 7TYO

Calcitonin gene-related peptide (CGRP) is a peptide that plays a crucial role in various physiological and pathological processes. CGRP is a member of the calcitonin family of peptides, which also includes calcitonin, adrenomedullin, and amylin. It is widely distributed in the central nervous system and the peripheral nervous system, with significant roles in the regulation of blood vessels, pain transmission, and the immune response.

Structure and Gene

CGRP is derived from the CALC1 gene located on chromosome 11 in humans. This gene also encodes for the hormone calcitonin through alternative splicing, producing two distinct mRNAs. CGRP itself exists in two forms, α-CGRP and β-CGRP, which are encoded by separate genes in humans. α-CGRP is more abundant and is primarily produced in neurons, while β-CGRP is found in the enteric nervous system. Both forms are 37-amino acid peptides, sharing a high degree of structural homology but differing slightly in their biological activity.

Function

CGRP plays a pivotal role in cardiovascular homeostasis, with vasodilatory properties that contribute to the regulation of blood pressure and blood flow. It acts as a potent vasodilator, expanding blood vessels and lowering blood pressure. In the nervous system, CGRP is involved in the transmission of pain and is linked to the pathophysiology of migraine headaches. It is released from sensory neurons and can trigger migraine attacks by causing vasodilation and inflammation in the meninges.

In addition to its cardiovascular and nociceptive functions, CGRP has been implicated in the immune system. It modulates immune responses and has anti-inflammatory effects, influencing the activity of various immune cells.

Clinical Significance

Given its role in migraine, CGRP has become a target for new therapeutic interventions. Monoclonal antibodies targeting CGRP or its receptor have been developed and approved for the prevention of migraine. These treatments offer a new approach for patients with frequent or chronic migraines, providing relief by blocking the action of CGRP and preventing migraine attacks.

Furthermore, the vasodilatory effects of CGRP have implications for cardiovascular diseases. Research is ongoing to explore the potential of CGRP-based therapies in treating conditions characterized by impaired blood flow, such as ischemic heart disease.

Research Directions

Research on CGRP continues to uncover its multifaceted roles in human physiology and disease. Studies are exploring its involvement in other conditions, such as osteoporosis, due to its relationship with calcitonin and bone metabolism. Additionally, the potential of CGRP in treating inflammatory diseases is an area of growing interest, given its anti-inflammatory properties.

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