Structure, Function and Expression of the Human Calcitonin/α-CGRP Gene
Calcitonin is a small peptide hormone (32 amino acids) synthesised and secreted in mammals by the C-cells of the thyroid (Foster et al., 1964). The physiological role of calcitonin in mammals appears to be the protection of the skeleton in times of calcium stress such as growth, pregnancy and lactation (Stevenson et al., 1979). In common with other small peptide hormones, molecular cloning and nucleotide sequence analysis of rat and human calcitonin mRNA (Atnara et al., 1982; Craig et al., 1982; Le Moullec et al., 1984) demonstrates that calcitonin mRNA encodes a precursor polyprotein. Within this precursor, calcitonin is flanked by amino and carboxy terminal peptides of as yet unknown function, from which calcitonin is proteolytically cleaved and amidated prior to secretion (see Craig et al., 1982). The human calcitonin gene is expressed at elevated levels ectopically in lung carcinoma (Coombes et al., 1974), and at grossly elevated levels in medullary thyroid carcinoma (Milhaud et al., 1974). Elegant studies on the structure and expression of the rat calcitonin gene have resulted in renewed interest in this gene. These demonstrate the generation by RNA processing of alternative mRNA species from a single gene in an apparently tissue-specific manner. The mRNAs encode polyproteins cleaved by post-translational events to yield either calcitonin or the calcitonin gene-related peptide (CGRP) (Amara et al., 1982). Subsequent immunocyto-chemical studies showed a wide distribution of rat CGRP-producing cells within discrete regions of the central and peripheral nervous system (Rosenfeld et al., 1983). This suggests a potential role as a neuromodulator or neurotransmitter molecule, a supposition which has led to detailed analyses in a number of laboratories of the structure, function and expression of rat and human calcitonin/CGRP gene(s).
KeywordsMedullary Thyroid Carcinoma Salmon Calcitonin CGRP Receptor Human Calcitonin Mesenteric Vasculature
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- Al-Kazwini, S.J., Craig, R.K., Holman, J.J. and Marshall, I. (1985). Human and rat calcitonin gene-related peptides are vasodilators in coronary and mesenteric vasculature. Br. J. Pharmac., Proc. Suppl., in press.Google Scholar
- Bates, R.F.L., Buckley, G.A. and McArdle, C.A. (1984). Comparison of the antinociceptive effects of centrally administered calcitonin and calcitonin gene-related peptide. Br. J. Pharmac., 82:295.Google Scholar
- Craig, R.K., Marshall, I., Paciorek, P. & Shepperson, N.B. (1986). Cardiovascular effects of human and rat calcitonin gene-related peptides in anaesthetised dog. Br. J. Pharmac., Proc. Suppl.Google Scholar
- Goth, A. (1973). Histamine released by drugs and chemicals. In Histamine and antihistamines ed. Schachter, M. Vol. I Int. Encyclopedia of Pharmacology and Therapeutics, section 74, Pergamon Press, London, p25.Google Scholar
- Morales-Aguilera, A. & Vaughan-Williams, E.M. (1965). The effects on cardiac muscle of β-receptor antagonists in relation to their activity as local anaesthetics. Br. J. Pharmac., 24:332.Google Scholar
- Steenbergh, P.H., Höppener, J.W.M., Zandberg, J., Van de Ven, W.J.M., Jansz, H.S. and Lips, C.J., (1984). Calcitonin gene-related peptide coding sequence is conserved in the human genome and is expressed in medullary thyroid carcinoma. J. Clin. Endocrinol. Metab., 59:358–360.PubMedCrossRefGoogle Scholar
- Tschopp, F.A., Henke, H., Petermann, J.B., Tobler, P.H., Janzer, R., Hokfelt, T., Lundberg, J.M., Cuello, C. & Fischer, J.A. (1985). Calcitonin gene-related peptide and its binding sites in the human central nervous system and pituitary. Proc. Natl. Acad. Sci. U.S.A., 82:248.PubMedCrossRefGoogle Scholar
- Williams, F.D., Ponder, B.A.J. and Craig, R.K. (1986). CGRP in human medullary carcinoma and C-cell hyperplasia — an immunohistochemical study. Clin. Endocrinol. submitted.Google Scholar