Calcitonin Gene-Related Peptide (CGRP) and Receptors

Abstract

Calcitonin gene-related peptide (CGRP) is a peptide derived from the alternative splicing of the calcitonin gene. It belongs to the CGRP family, which also includes adrenomedullin, amylin, and intermedin. It is widely expressed in both central and peripheral nervous systems and thus possesses diverse biological effects, including the modulation of sensations (smell, taste, audition, vision, nociception), learning and memory, food intake, autonomic functions, skeletal muscle motility, vasodilation, immune and inflammatory responses, and gastrointestinal tract functions. CGRP is suggested to be involved in the pathogenesis of diseases such as migraine, diabetes, pain, and inflammation. Two isoforms (α and β) of CGRP have been identified and are encoded by two different genes. CGRP-induced biological effects are mediated via specific receptors, which are composed of the calcitonin receptor-like receptor and other component proteins such as the receptor activity-modifying protein 1 and the receptor complement protein (RCP). CGRP and its receptors are particularly enriched in the lateral hypothalamic area and in primary sensory neurons, as well as in cranial and spinal motor neurons. Drugs modulating CGRP and its receptors should prove beneficial in the treatment of various disorders, such as migraine, as recently demonstrated using BIBN4096BS, a nonpeptidic CGRP receptor antagonist.