Calcitonin

Mechanism (as reported)

Research described calcitonin-family peptides as signaling through type II GPCRs, with calcitonin receptor subtypes and related receptor interactions discussed as part of a GPCR family. Structural studies/reviews reported a conserved N-terminal disulfide-bridged ring and amidated C-termini among homologous related peptides (calcitonin, CGRP, adrenomedullin, amylin).

Key findings (each cites a source)

• A study/review reported that calcitonin, calcitonin gene-related peptide (CGRP), adrenomedullin, and amylin are structurally related homologous peptides with N-terminal 6–7 amino acid ring structures linked by a disulfide bridge and with amidated C-termini, and that calcitonin receptor structures and subtypes have been identified via molecular cloning. [PMID 7627335]
• A study/review reported cross-reaction and overlapping biological actions among receptors for calcitonin, CGRP, adrenomedullin, and amylin, suggesting these receptors belong to a family of G-protein-coupled receptors including those of parathyroid hormone, secretin, and vasointestinal peptide. [PMID 7627335]
• A review reported that calcitonin-derived peptide carrier sequences (derived from human calcitonin) can translocate different bioactive molecules across cellular membranes, and described development from full-length hormone (noted in the review context as therapeutic nasal administration) through N-terminally truncated fragments to branched carrier peptides. [PMID 18160173]
• A review reported that calcitonin receptor-stimulating peptide (CRSP) shows high sequence identity with CGRP but distinct biological properties, and categorized CT/CGRP/CRSP peptides into a family based on evolutionary and genomic organization comparisons. [PMID 19540291]
• A review reported that CRSP genes were identified in mammals such as pigs and dogs of Laurasiatheria, but not in primates and rodents of Euarchontoglires, with multiple CT/CGRP/CRSP family gene copies suggested across placental mammal lineages. [PMID 19540291]
• An article reported that calcitonin was originally identified and isolated from teleosts and that calcitonin/intermedin family peptides share a conserved N-terminal disulfide-bridged ring structure and signal through type II GPCRs, with three unique receptor activity-modifying proteins noted in that report. [PMID 15476930]
• The same article reported identification of a novel calcitonin/CGRP family peptide named intermedin and provided comparative discussion of calcitonin-family peptide gene evolution across vertebrate genomes, including human gene paralogs and teleost genome copies. [PMID 15476930]
• A paper described development and evaluation of oral calcitonin formulations and reported that an oral preparation combining the active peptide hormone with a caprylic acid derivative was developed to enhance bioavailability; it also reported ongoing clinical trials in osteoarthritis and that a phase 3 study did not demonstrate significant vertebral fracture reduction, with the clinical program for osteoporosis under review. [PMID 22281725]
• A methods paper reported a high-throughput UHPLC-HRMS-based workflow for peptide mapping and amino acid sequencing for Calcitonin Salmon injection, including addressing challenges from phenol in the product matrix and achieving 100% protein coverage with automated b/y ion annotation and identifications based on MS/MS spectra. [PMID 38479303]
• A review reported structural and biological properties of three calcitonin receptor-stimulating peptides (CRSP-1, CRSP-2, CRSP-3), including that CRSP-1 is described as a specific ligand for the calcitonin (CT) receptor and is expressed/synthesized mainly in the CNS, pituitary, and thyroid gland, with discussion of in vivo effects on plasma calcium concentration in rats. [PMID 15501538]