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Results for “Calcitonin”

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At least 19 recordsLinked to original sources
PubMed1992

N-terminal truncation of salmon calcitonin leads to calcitonin antagonists. Structure activity relationship of N-terminally truncated salmon calcitonin fragments in vitro and in vivo.

Structural requirements for binding to the bone calcitonin (CT) receptor and for CT bioactivity both in vitro and in vivo were assessed for a series of N-terminally truncated, N alpha-acetylated, fragments of salmon calcitonin (sCT). Sequential deletion of amino acid residues from the amino-terminus of [Ala7]sCT-(2-32) peptide amide first led to partial agonists and, upon deletion of residues 1 to 7, to a high affinity antagonist, N alpha-acetyl-sCT-(8-32)-NH2. The presence of two separate domains within the sCT sequence is proposed: (I) a binding domain comprising residues 9-32 and (II) an activation domain requiring residues 3 to 6. N alpha-acetyl-sCT-(8-32)-NH2, in several bioassays including plasminogen activator release from LLC-PK1 cells (pA2 = 7.31), cAMP production in UMR-106-06 cells (pA2 = 7.81) and in the fetal rat long bone resorption assay showed potent antagonistic properties.

Acetylation↗
PubMed1977

Stability of [Asu1,7]-eel calcitonin and eel calcitonin in vitro and in vivo.

Stability of [Asu1,7]-eel calcitonin was compared with that of eel calcitonin by the radioimmunoassay method. [Asu1,7]-Eel calcitonin cross-reacted with anti-eel calcitonin antisera. [Asu1,7]-Eel calcitonin was as stable as eel calcitonin in rabbit liver or rabbit kidney extracts when incubated at 37 degrees C. Disappearance curves from the plasma of [Asu1,7]-eel calcitonin and eel calcitonin following iv injection in rabbits were quite similar.

Animals↗
PubMed1977

Calcitonin-responsive adenylate cyclase in a calcitonin-producing human cancer cell line.

A calcitonin-responsive adenylate cyclase has been found in a cell line of a poorly differentiated bronchial carcinoma (BEN cells). The cells have previously been shown to secrete an immunoreactive form of calcitonin in culture. Salmon calcitonin (SCT), porcine calcitonin (PCT) and human calcitonin (CT-M) all stimulated adenylate cyclase activity in particulate preparations. CT-M sulphoxide had little effect. The concentrations of the calcitonins required for half the maximum activation of adenylate cyclase were 6-8, 18 and 90 nm respectively. SCT (30pm) and CT-M (60 pm) increased the intracellular concentration of cyclic AMP from 11-2+/-0-2 (s.e.) to 18-2+/-0-2 and 16-7+/-0-2 respectively over a 2-5-min period. SCT (labelled with 125I) bound to particulate preparations of Ben cells, and competition for binding occurred with unlabelled SCT and CT-M. The concentration of SCT required for half the maximum inhibition of [125I]SCT binding was 11 nm. CT-M sulphoxide inhibited only at high concentration (3 micron). The characteristics of the adenylate cyclase response to SCT did not change over the period between cell adhesion (after subculture) and confluence. However, pre-incubation of cells for 4 h with SCT (150 nm) abolished the subsequent adenylate cyclase response of particulate preparations to further hormone. The practical difficulties encountered in purifying and quantifying the large-mol.-wt. form of CT-M secreted by BEN cells has precluded direct investigation of the potential relationship between hormone secretion and the occurrence of the calcitonin receptor. This relationship is discussed in terms of its possible biological significance.

Adenylyl Cyclases↗
PubMed1975

Renal receptors for calcitonin: coordinate occurrence with calcitonin-activated adenylate cyclase.

High affinity binding of 125I-labeled salmon calcitonin ([125I]SCT) and calcitonin-activated adenylate cyclase were detectable in renal plasma membranes from the rat. Addition of 5'-guanylyl-imidodiphosphate lowered the threshold for enzyme activation by peptide hormones. Renal plasma membranes from man, dog and cow contained little or no calcitonin-sensitive adenylate cyclase and showed no high affinity binding of [125I]SCT. High affinity binding sites were distributed during membrane fractionation in fractions where the specific activity of hormone-sensitive adenylate cyclase was greatest. Calcitonin binding and activation of the adenylate cyclase enzyme occurred at similar hormone concentrations. The relative potencies of calcitonin analogues were similar whether measured by competition for high affinity binding sites or by effect on adenylate cyclase. Low concentrations of Lubrol-PX, a nonionic detergent, did not affect catalytic function of the enzyme determined in the presence of sodium fluoride but caused parallel loss of high affinity [125I]SCT binding and hormonal sensitivity of the enzyme. This observation provided further evidence that interaction of calcitonin with specific receptors (identified with [125I]SCT binding) is essential for calcitonin activation of adenylate cyclase, but showed that catalytic activity of enzyme does not require functioning hormone receptors.

Adenylyl Cyclases↗
PubMedDate not supplied

Assessment of thyroidal "C" cell secretion in osteoporotic girls with Turner's syndrome. Basal and calcium-stimulated levels of total calcitonin, extractable calcitonin and katakalcin.

Osteoporosis is a common finding in Turner's syndrome. To test the hypothesis that calcitonin deficiency may contribute to bone mineral loss in Turner's syndrome, we studied basal and calcium-stimulated (2 mg/kg body weight in 5 min) levels of total calcitonin, extractable calcitonin and katacalcin in 15 girls with Turner's syndrome and osteoporosis. Fifteen age-matched healthy girls were studied as controls. Both basal calcitonin (total and extractable) and katacalcin values were not significantly different in patients with Turner's syndrome in comparison with those of the controls. The calcium stimulation test showed a similar "C" cell secretory reserve in both groups. The calculation of delta CT/delta iCa of total and extractable calcitonin and delta KC/delta iCa, which accounts for individual variations in serum ionized calcium increases, did not show any significant difference between girls with Turner's syndrome and controls. We conclude that calcitonin deficiency is not a causative factor of osteoporosis in girls with Turner's syndrome and that in this syndrome long-life estrogen deficiency does not impair "C" cell secretory activity.

Adolescent↗
PubMed1992

Immunohistochemical comparison of chromogranins A and B and secretogranin II with calcitonin and calcitonin gene-related peptide expression in normal, hyperplastic and neoplastic C-cells of the human thyroid.

Normal and hyperplastic thyroid C-cells and 14 cases of medullary thyroid carcinoma were investigated immunohistochemically with antibodies against chromogranins A and B, secretogranin II, calcitonin and calcitonin gene-related peptide (CGRP). Normal and hyperplastic C-cells showed strong calcitonin and chromogranin A immunoreactivity whereas CGRP, chromogranin B and secretogranin II expression was less intense. Strong calcitonin and chromogranin A immunoreactivity was also found in the majority of tumour cells in medullary thyroid carcinoma. The CGRP, chromogranin B and secretogranin II staining observed was present in variable patterns. In some cases CGRP, chromogranin B and secretogranin II could only be demonstrated in isolated tumour cells with elongated processes suggestive of neuronal differentiation of these cells. The biological function(s) of the chromogranins/secretogranins remain(s) still unclear. There is evidence that these proteins are pro-peptides which give rise to functionally active compounds. Studies on normal C-cells and medullary thyroid carcinoma may elucidate the role of chromogranins/secretogranins in endocrine and neuronal cells.

Adult↗
PubMed1975

Radioimmunoassay for human calcitonin employing synthetic calcitonin M: its clinical application.

A sensitive and reliable radioimmunoassay for human calcitonin was described and applied to preliminary clinical studies. 125I-labelled synthetic human calcitonin M was purified by gel filtration with Sephadex G-25 and G-100. A nonequilibrium incubation system was applied at the final volume of incubation mixture of 500 mul, in which pooled plasma from normal subjects or hormone free serum was used as carrier protein at 20% incubation mixture. Dextran T 40 coated charcoal, resuspended in 1% bovine serum albumin buffer, was used for the separation of free from bound tracer. This showed the least nonspecific adsorption of tracer to charcoal. The assay was sensitive to 0.1 ng per milliliter of plasma. Recovery of synthetic human calcitonin added to plasma was found to be 101% (S. D., +/- 8). Diluted plasma from a patient with medullary thyroid carcinoma showed a dilution curve parallel to standards. Basal calcitonin levels were less than 0.3 ng/ml in normal subjects. Relatively high values were found in patients with chronic renal failure and in patients with malignant tumors. Extremely elevated values were found in patients with medullary thyroid carcinoma. Provocative calcium infusion tests were also performed.

Bone Neoplasms↗
PubMed1977

[Calcitonin in the ultimobrancial body of Anguilla (Anguilla anguilla L.): cytologic localization by indirect immunofluorescence using human anti-salmon-calcitonin antibodies].

The localization of intracellular calcitonin has been achieved by immunofluorescence in the cytoplasm of all cells forming the epithelium of the ultimobranchial body of eels, using a human antiserum against synthetic Salmon calcitonin I. The specificity of the reaction is demonstrated by inhibition with synthetic salmon calcitonin (S.C.T.); the fluorescence is not inhibited by synthetic human calcitonin (H.C.T.).

Anguilla↗
PubMed1992

Effects of calcitonin and calcitonin gene-related peptide on 3H-thymidine incorporation into DNA of rat thyroid lobes in vitro.

The effects of a 4 h incubation of rat thyroid lobes, in the presence of calcitonin (CT) and calcitonin gene-related peptide (CGRP) on the incorporation of 3H-thymidine into DNA, were investigated. In other groups the thyroid lobes were incubated during exposure to CT and thyrotropin (TSH), and to CGRP together with TSH. All concentrations of CT (10(-6)-10(-8) M) revealed a tendency towards lowering 3H-thymidine uptake, but the effect was not statistically significant. The influence of CGRP was dose-dependent; the lowest concentration of CGRP (10(-9) M) significantly enhanced DNA synthesis in the incubated rat thyroids; an intermediate dose of the peptide (10(-8) M) had no effect, while the highest concentration of CGRP (10(-7) M) decreased 3H-thymidine incorporation. Calcitonin (10(-7) M), as well as CGRP (10(-8) M), suppressed the stimulatory effect of TSH on 3H-thymidine incorporation.

Animals↗
PubMedDate not supplied

Calcitonin and the bone fluid compartment: effect of calcitonin and/or parathyroid hormone on plasma radiocalcium changes.

Changes in plasma calcium and 45Ca concentrations were followed after injection of calcitonin or a combination of calcitonin (CT) and parathyroid hormone (PTH) into thyroparathyroidectomized rats maintained on thyroxine. Comparison was made between rats injected with the hormone(s) after a recent feeding and after an overnight fast. Also cor (18 hr 45Ca) before, and more than 6 days (greater than 6 day 45Ca) prior to hormone administration. The following results were obtained: The action of CT predominated over that of PTH for the first few hours after injection. However, the effects of PTH were eventually manifested even when additional CT was administered. In the "greater than 6 day" 45Ca groups, PTH normally produced an increase in plasma 45Ca specific activity. However, in fasted rats, plasms 45Ca fell with total calcium with no change in specific activity following CT injection. In fed rats CT injection was followed by a decrease in plasma 45Ca specific activity. When both hormones were administered plasma 45Ca specific activity changes mimicked those produced by CT alone even after PTH plasma effects were manifested. In the "18 hr" 45Ca groups, CT produced first a drop in plasma 45Ca, followed by a reduction in the rate of its removal from plasma. It is concluded that the data can best be explained by the postulate that plasma calcium concentrations are maintained by the control of fluxes between bone fluid in the osteocyte-lining cell bone unit and the extracellular fluid. PTH increases the efflux from this bone fluid compartment while CT restricuts the source of calcium and, therefore, the efflux. Plasma 45Ca changes are due to a combination of changes in flux rates and mixing processes between the extracellular fluid compartment and the bone fluid compartment.

Animals↗
PubMed1992

Transforming growth factor-beta enhances calcitonin-induced cyclic AMP production and the number of calcitonin receptors in long-term cultures of human umbilical cord blood monocytes in the presence of 1,25-dihydroxycholecalciferol.

Transforming growth factor-beta (TGF-beta) is a multifunctional polypeptide, abundant in bone, that regulates both proliferation and differentiation of a wide variety of cells, but its role in osteoclast differentiation remains controversial. We have recently shown that long-term cultures of human cord blood monocytes, in the presence of 1,25 dihydroxycholecalciferol (1,25-(OH)2D3), give rise to cells that express two markers of the osteoclast phenotype, namely, the vitronectin receptor (VNR) and the calcitonin receptor (CTR). TGF-beta enhanced the proportion of cells expressing the VNR. In the present study, we investigated the effect of TGF-beta on the expression of CTR in cord blood monocytes cultured during 3 weeks in the presence of 1,25-(OH)2D3. When added within the first 2 weeks of culture, TGF-beta (500 pg/ml) significantly decreased the cell protein content. TGF-beta alone did not stimulate basal cAMP production. The 10 nM-sCT-stimulated cAMP production was enhanced by increasing TGF-beta concentrations from 50 pg/ml to 1,000 pg/ml: for 500 pg/ml TGF-beta, it was 294 +/- 28% vs. 140 +/- 25% for control cultures (p less than 0.01). The sCT dose-response curves showed a higher cAMP production from 10(-9) M to 10(-7) M of sCT in the presence of 500 pg/ml TGF-beta than in control cultures. The increase was 325 +/- 36% in the presence of TGF-beta and 195 +/- 13% in the absence of TGF-beta, for 10(-7) M sCT (p less than 0.01). This effect of TGF-beta on cAMP production was not observed either when it was added to monocyte cultures the last day or 2 hours before the end of the culture or in MCF7, a human breast cancer cell line that expresses CTR. [125I]-sCT binding studies performed on confluent cells showed similar Kd in control and TGF-beta-treated cells. By contrast, the CTR number was significantly increased in the presence of TGF-beta: 6.1 +/- 2 x 10(4) receptors per cell in control cultures and 28.8 +/- 8.1 x 10(4) receptors per cell in TGF-beta-treated cultures (p less than 0.05). It is thus suggested that TGF-beta increases the number of CTR of these cells that have other features of preosteoclasts. The role of this cytokine on the process of osteoclast differentiation and in bone resorption is thus emphasized.

Autoradiography↗
PubMed1978

Radioimmunoassay of human calcitonin using labeled [Asu1, 7]-human calcitonin analogue.

Application of synthetic human calcitonin analogue ([Asul,7]-hCT) was attempted, since it is chemically more stable than native hCT. [Asu1, 7]-hCT was successfully labeled with 125I to a specific activity ranging from 410 to 540 microCi/microgram. Sensitivity, recovery and reproducibility of the assay system using 125I-labeled [Asu1,7]-hCT analogue, standard synthetic hCT and its antibodies, were 49 pg/ml, 99.8 +/- 4%, and 7.95% (C. V. within assay) or 21.9% (C. V. between assays), respectively. The dilution curve of the sera obtained from patients with medullary carcinoma paralled well with the standard curve. 125-I-labeled [Asu1, 7]-hCT analogue can be used for routine radioimmunoassay of hCT.

Animals↗
PubMed1992

Comparison of a calcitonin gene-related peptide receptor in a human neuroblastoma cell line (SK-N-MC) and a calcitonin receptor in a human breast carcinoma cell line (T47D).

A specific CGRP-binding protein of M(r) 60,000 has been identified in the human neuroblastoma cell line SK-N-MC. After N-deglycosylation a M(r) of 48,000 was found. The M(r) were indistinguishable from those determined in the human cerebellum. Receptor binding of CGRP is coupled to cyclic AMP formation. The latter is antagonized by hCGRP-I8-37. CT and DAPamide interact only minimally with the CGRP receptor, whereas CGRP and DAPamide are full agonists in T47D cells. The CT receptor on human breast cancer cell line T47D is clearly different from the human CGRP receptor.

Amino Acid Sequence↗