Novel peptides from the calcitonin gene: expression, receptors and biological function

Calcitonin gene products include calcitonin and its carboxyl-terminal flanking peptide (in man PDN-21), and calcitonin gene-related peptide (CGRP). Alternative splicing of the initial gene transcripts results in the production of two distinct messenger RNA encoding precursors of CGRP and of calcitonin. CGRP messenger RNA is the predominant transcription product of the calcitonin gene in neural tissues, but it is also present in the pituitary and the C-cells of normal thyroid glands and in medullary thyroid carcinoma. Immunoreactive CGRP has, moreover, been recognized around blood vessels of the heart. Calcitonin and PDN-21 are cosecreted from thyroid C-cells, but they are also found in the brain and pituitary. CGRP receptors are present in the brain and the heart, and calcitonin receptors in bone and kidney cells and in the hypothalamus. Calcitonin administered peripherally and in vitro inhibits bone resorption and stimulates renal 1.25-dihydroxycholecalciferol production. CGRP used in the same manner has potent cardiovascular effects (vasodilation, hypotension, positive chronotropic and inotropic action in the heart). Intracerebroventricular administration of CGRP raises the blood pressure, and both CGRP and calcitonin inhibit gastric acid secretion and food intake. The distinct but overlapping effects of calcitonin and CGRP raise important regulatory and functional issues.