title: A neuroendocrine peptide derived from the amino-terminal half of rat procalcitonin.
abstract: The sequence of rat procalcitonin reveals that calcitonin is located within the precursor's midregion, flanked by two potential polybasic cleavage sites that separate it from amino- and carboxyl-terminal domains. Cleavage at the polybasic sites during precursor processing to generate the 32-residue calcitonin should also generate 57- and 16-residue peptides from the amino- and carboxyl-terminal flanking regions. The carboxyl-terminal flanking hexadecapeptide and its coordinate secretion from C cells with calcitonin have been previously reported. In the present study we have focused on the predicted 57-residue amino-terminal procalcitonin cleavage peptide (N-proCT). We raised antisera to synthetic peptides homologous to the carboxyl- and amino-terminal regions of the putative 57-amino-acid N-proCT and screened calcitonin-rich neoplastic and nonneoplastic C-cells for these two immunoreactivities. A single species of 7.4 kilodaltons detected in C cells by gel filtration and reversed-phase HPLC analyses accounts for most of the carboxyl- and amino-terminal immunoreactivities and possesses the biochemical and biological features predicted for N-proCT. When C cell hyperplasia is induced by a high fat diet, thyroidal levels of calcitonin and N-proCT increase in parallel. In neoplastic C cell cultures, N-proCT and calcitonin concentrations are nearly equimolar in both cellular extracts and basal medium; dexamethasone increases both the cellular and secreted concentration of these peptides. Basal and dexamethasone-treated cultures show calcium-dependent, parallel secretion of N-proCT and calcitonin. Thus, the 57-residue N-proCT predicted from analysis of the procalcitonin sequence is a secretory peptide that appears to be present in equimolar amounts and coordinately regulated with calcitonin in vivo and in vitro.
authors.affiliation: Department of Medicine, University of Washington, Seattle 98195.
authors.forename: D M
authors.initials: DM
authors.lastname: Burns
authors.forename: R S
authors.initials: RS
authors.lastname: Birnbaum
authors.forename: B A
authors.initials: BA
authors.lastname: Roos
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D002116:Calcitonin / Q000032:analysis* / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide; D002277:Carcinoma / Q000032:analysis; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006965:Hyperplasia; D007106:Immune Sera / Q000276:immunology; D010446:Peptide Fragments / Q000032:analysis* / Q000378:metabolism; D011498:Protein Precursors / Q000032:analysis* / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D013961:Thyroid Gland / Q000032:analysis* / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000032:analysis; D014407:Tumor Cells, Cultured
chemical_list: C000606591:Calca protein, rat; D007106:Immune Sera; D010446:Peptide Fragments; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide