243 Introduction 474 Discussion 1165 Non standard abbreviations: AMY, amylin receptor phenotype; CGRP, calcitonin gene-related peptide; CLR, calcitonin receptor-like receptor; CT, calcitonin; CTR, calcitonin receptor; GPCR, G protein-coupled receptor; HA, haemagglutinin epitope tag; hCT, human calcitonin; RAMP, receptor activity modifying protein; rAmy, rat amylin; sCT, salmon calcitonin; TMD, ...

cDNA analyses predict that the human calcitonin gene encodes the two precursor proteins of calcitonin and calcitonin gene-related peptide (CGRP). The mRNAs for the putative precursors of these peptides are derived from alternative processing of the primary transcript of this gene. The 75 amino-terminal residues of each preprohormone are predicted to be identical. We have developed the TT human ...

Using a sensitive radioimmunoassay, we detected human immunoreactive calcitonin in cell extracts and in cell-exposed media of the HL60 cell line derived originally from a patient with acute promyelocytic leukemia. The cell extract was chromatographed on a reverse-phase high-pressure liquid chromatography system. Radioimmunoassay of the fractions showed that the immunoreactive calcitonin was het...

A photoaffinity derivative of salmon calcitonin has been produced by transglutaminase-mediated incorporation of N-(beta-aminoethyl)-4-azido-2-nitroaniline into the hormone. The derivative, purified by high pressure liquid chromatography, retained the abilities to bind to cultured T47D breast cancer cells and to stimulate adenylate cyclase in these cells. In both these respects it was equipotent...

Calcitonin and ·-CGRP are products of the alternatively spliced gene CALCA. Calcitonin (CALC) mRNA is predominantly found in thyrodial C cells and mRNA encoding the neuropeptide calcitonin gene-related peptide (CGRP) in neural tissues (Amara et al., 1982, Rosenfeld et al., 1983). In vivo, calcitonin reduces serum calcium and acts as an antagonist to the parathyroid hormone. The human CALC-A/·-C...

Twenty-three out of 28 patients with metastatic breast carcinoma and one out of 13 patients with localised disease had raised levels of plasma immunoreactive calcitonin. Monolayer cultures of breast carcinomas maintained for up to 10 weeks released immunoreactive calcitonin, and a primary breast carcinoma passaged in "nude" mice for over a year contained material immunologically and chromatogra...

Calcitonin inhibits both osteoclast formation and bone resorption, and is a primary treatment for patients with hypercalcemia and increased bone turnover. However, the clinical utility of calcitonin is limited because patients become refractory to calcitonin after several days (the calcitonin "escape phenomenon"). The molecular basis for calcitonin "escape" is unclear. To determine the regulato...

Receptors for the hypocalcaemic hormone, calcitonin (CT), have been identified in a membrane fraction prepared from term human placentae. Binding of 125I-labelled salmon CT (125I-sCT) to the membranes was time- and temperature-dependent, saturable (Bmax. 58 +/- 11 fmol/mg of protein), of high affinity (Kd 80 +/- 21 pM) and poorly reversible. Species-specific CTs and CT analogues competed for 12...