Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T47D cells possess specific calcitonin (CT) receptors and a CT-responsive adenylate cyclase. Internalization of part of their CT receptors has been suggested. At 37 degrees C, bound 125I-labelled salmon CT (sCT) becomes increasingly resistant to acid washing, which can remove surface-bound hormone, thus indicating internalization. Monensin and chloroquine, which raise the pH of the lysosomes and thereby inhibit cellular processing of endosomes, inhibit the decrease of total bound activity seen in the controls. Acid-resistant (internalized) activity increases to the levels of total binding. Preincubation with sCT leads to a loss of specific binding. Recovery of CT binding is prevented by monensin, which also inhibits transport of cellular proteins to the cell membrane. Recovery is not influenced by chloroquine. As chloroquine prevents recycling, we conclude that after binding of CT the receptors are internalized, transferred to a lysosomal compartment, and degraded intracellularly without recycling. All receptors seem to undergo internalization. Desensitization to CT in T47D cells is at least partly mediated by intracellular metabolism of CT receptors.
Mol Cell Endocrinol 1988 Jul
PMID:Down-regulation of calcitonin receptors in T47D cells by internalization of calcitonin-receptor complexes. 285 Feb 44

We report the visualization of calcitonin gene expression products at the mRNA and peptide levels on the same section of a medullary thyroid carcinoma by combined in situ hybridization and immunohistochemistry. mRNA detection was accomplished by hybridization with radioactively labeled antisense RNA probes followed by autoradiography and immunohistochemically using the avidin-biotin complex method. Best results were obtained when in situ hybridization preceded immunohistochemistry, as determined by quantitative analysis of the autoradiographs. When immunohistochemistry was performed prior to in situ hybridization, the RNase inhibitor heparin had to be added to the antibodies to retain hybridizable mRNA. The intensity of the two reactions varied in individual cells, indicating a functional heterogeneity of tumor cells with regard to calcitonin mRNA content and storage of the related immunoreactive peptide. These results, in combination with elevated serum calcitonin levels, suggest significant differences in the rate of secretion of individual tumor cells. Simultaneous localization of mRNA and its peptide within the same cell may, therefore, provide further insight into gene expression and secretory activity at the single cell level.
Virchows Arch B Cell Pathol Incl Mol Pathol 1987
PMID:Simultaneous localization of calcitonin mRNA and peptide in a medullary thyroid carcinoma. 289 88

We have carried out an electron microscopic and immunocytochemical study of thyroid medullary carcinoma arising spontaneously in the Djungarian hamster, Phodopus sungorus. At the ultrastructural level the cytoplasm of tumor cells contained numerous round to slightly elongated, dense-cored secretory granules. The number of secretory granules differed from cell to cell in the tumor, being scanty in some cells but more or less abundant in most. Electron microscopic-immunocytochemistry demonstrated that all dense-cored secretory granules in all tumor cells exhibited calcitonin immunoreactivity. In approximately 10% of the tumor cells, unusual star-shaped secretory vesicles were also found in the cytoplasm. These vesicles contained a small, but well-defined, lucent core surrounded by a region of finely granular material of greater electron density. The outer contour of these unusual vesicles was stellate rather than smooth. They appeared to originate not from the Golgi complex, but from the rough endoplasmic reticulum. These atypical stellate vesicles did not show any calcitonin immunoreactivity. Furthermore, in a small number of tumor cells (approximately 1%) a third type of membrane enclosed structure was found. These were conspicuous rods 1-5 micron in length with tapering ends and a crystalline substructure. The presence of both normal and atypical secretory granules in some tumor cells suggests that carcinogenic transformation may interfere with the normal synthesis and assembly of secretory products by the cell.
Virchows Arch B Cell Pathol Incl Mol Pathol 1988
PMID:Thyroid medullary carcinoma of the Djungarian hamster Phodopus sungorus. Ultrastructural evidence for the production of normal and atypical intracellular granules. 289 41

Hormone secretion from single, rat pancreatic B cells was visualised by a reverse haemolytic plaque assay for C-peptide. Quantitative analysis of the size and number of haemolytic plaques indicated that exposure to 3, 5, 10 and 20 mM glucose resulted in a dose-dependent increase in both the magnitude of C-peptide, and thus, insulin release by individual B cells and the recruitment of activity secreting B cells. Somatostatin and calcitonin gene-related peptide, fragment 28-37 (CGRP28-37) were shown to inhibit glucose-stimulated insulin release as assessed by the size of individual plaques and the number of recruited B cells, and hence to reduce the total area of plaques formed. In the presence of 15 mM glucose, a dose-dependent effect of CGRP28-37 on the secretion of insulin was observed, with the size of plaques formed by individual B cells reduced at concentrations of CGRP28-37 between 10(-5) and 10(-11) M. Thus, both somatostatin and CGRP28-37 can act directly on individual B cells to inhibit their secretory response to increasing levels of glucose. We suggest that these peptides which can be immunolocalised in islet cells may have a role in the regulation of insulin secretion.
Mol Cell Endocrinol 1988 May
PMID:Calcitonin gene-related peptide and somatostatin inhibit insulin release from individual rat B cells. 289 26

Calcitonin (CT) and the calcitonin gene-related peptide (CGRP) are generated by alternative RNA processing from a single CT/CGRP gene. Recently, we reported the existence of CGRP-immunoreactivity and CGRP mRNA in endocrine cells or Kulchitsky (K) cells of human and rat lung [Wada et al. 1987b]. In this report, an examination was made of developmental changes in the expression of the CGRP gene in rat lungs by immunohistochemistry, radioimmunoassay (RIA) and Northern hybridization. CGRP-positive K-cells in lung tissue appeared on the 18th day of gestation. Their number was greatest on the 20th day of gestation and then decreased postnatally. The level of CGRP in rat lung was found to be highest in a 1-day-old neonate by RIA. In the Northern hybridization of rat lung using the CGRP 3' non-coding region (exon 6) of the first human CT/CGRP gene as the probe, 1.0 kilobase (kb) CGRP mRNA was found to be abundant on the 20th day of gestation and in a 1 day-old neonate. It thus appears that CGRP in rat lung is essential for pulmonary adaptation at birth and/or from the last intrauterine stage to the early neonatal period.
Virchows Arch B Cell Pathol Incl Mol Pathol 1988
PMID:Developmentally regulated expression of the calcitonin gene related peptide (CGRP) in rat lung endocrine cells. 290 May 74

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.
Mol Endocrinol 1989 Jan
PMID:A neuroendocrine peptide derived from the amino-terminal half of rat procalcitonin. 291 45

We have produced monoclonal antibodies which bind specifically to mouse bone cells and then selected these monoclonal antibodies for their ability to inhibit parathyroid hormone (PTH) responses in mouse cranial bone treated with the (1-34) amino terminal peptide of bovine PTH [bPTH(1-34)]. One clone, designated 3-6, characterized as an IgM(kappa), significantly inhibited the accumulation of cAMP in response to bPTH(1-34) at concentrations of hormone between 10(-9) and 10(-7) M. This antibody was subsequently isolated by gel filtration and shown to bind to intact mouse calvariae, with saturation binding occurring at 3 micrograms/ml IgM. A maximal inhibition of approximately 70% of the cAMP accumulation produced in response to 2.5 X 10(-9) M (100 ng/ml) bPTH(1-34) was obtained with 7 micrograms/ml of the purified 3-6 IgM. At this concentration of 3-6 IgM, the half-maximal dose of PTH for activation of cAMP accumulation was increased from 5 X 10(-9) M to 2 X 10(-8) M with no reduction in maximal levels of cAMP production. The utility of this antibody as an inhibitor was further tested by its ability to block the binding of an iodinated PTH analogue, 125I-[Nle8, Nle18, Tyr34]-bPTH(1-34) to mouse cranial bone. The 3-6 IgM at a concentration of 5 X 10(-8) M inhibited 70% of the specific binding of the 125I-labeled analogue. In the absence of parathyroid hormone, 2 X 10(-8) M 3-6 IgM produced a 4-fold increase in cAMP above basal levels, as compared to 40-fold maximal increases observed with PTH, indicating a partial PTH agonist activity of this antibody. When tested for effects on other hormones, 3-6 IgM did not inhibit cAMP accumulation produced in response to salmon calcitonin, epinephrine, prostaglandin E2 or cholera toxin. We propose that the 3-6 monoclonal IgM is specific for the PTH receptor or a component of the PTH receptor-adenylate cyclase system and that this or similar antibodies will serve as useful reagents for future molecular characterization of this receptor.
Mol Cell Endocrinol 1985 Jul
PMID:Identification of a monoclonal antibody which interacts with the parathyroid hormone receptor-adenylate cyclase system in murine bone. 299 Oct 44

The present study examined the influence of the calcium ionophores A23187 and X537A on the calcitonin (CT) secretory process. The isolated perfused porcine thyroid was used to evaluate ionophore effects on CT secretion and thyroid slices were used to measure 45Ca uptake. Both A23187 and X537A enhanced the rate of CT release from the perfused thyroid. A23187 at a concentration of 19 microM (10 micrograms/ml) produced a maximal increase in CT secretion of 325% above control levels. X537A at a concentration of 16 microM (10 micrograms/ml) produced a peak rise in CT release of approximately 2000% over control levels. The CT secretory response to A23187 was found to be completely calcium dependent; however, the secretory response to X537A was partially, but not completely dependent upon the presence of perfusate calcium. The results demonstrate that these calcium ionophores are very potent CT secretagogues which vary considerably in their calcium dependency.
Mol Cell Endocrinol 1986 Apr
PMID:Influence of the calcium ionophores A23187 and X537A on calcitonin secretion from the isolated perfused porcine thyroid. 308 20

We have investigated the acute effects of elevated plasma potassium concentrations on the calcitonin (CT) mRNA level measured by dot-blot hybridization. Plasma CT levels were significantly increased (X2) 30 min after potassium administration (1.2 mmol, KCl/100 g body weight) in adult female rats; a trend towards increased values was observed 10 min after treatment. No change in plasma calcium concentration was induced by the elevated extracellular potassium levels. The amount of CT mRNA measured by dot-blot hybridization was statistically significantly increased 10 min and 30 min (around 47-55%) after potassium treatment. This finding was confirmed by a Northern blot analysis. It is suggested for the first time that the potassium-induced CT release is associated with a slight increase in CT mRNA level. The increased CT secretion was probably mediated through a rise in the ionized calcium concentration of the C-cell.
Mol Cell Endocrinol 1988 Oct
PMID:Potassium administration and calcitonin mRNA level in the rat. 318 19

Expression of the calcitonin (CT)/calcitonin gene related peptide (CGRP) gene and the proopiomelanocortin (POMC) gene has been demonstrated by Northern blot hybridization analysis of RNA extracted from human medullary thyroid carcinoma (MTC), pheochromocytoma and lung carcinoma. CT mRNA in these tumors could not be distinguished in size from CT mRNA isolated from normal human thyroid tissue. CGRP mRNA (previously demonstrated in 12 out of 12 lung tumor cell lines investigated) could not be detected in 13 primary lung tumors or 10 metastases thereof. The length of POMC mRNA in MTCs (present in all 4 metastases investigated but not in 7 primary tumors) and pheochromocytomas is about 100 nucleotides more than pituitary POMC RNA. In lung tumors 2 POMC RNA species can be detected, one of the same size as in pituitary tissue and one about 100 nucleotides larger.
Mol Cell Endocrinol 1986 Sep
PMID:Detection of mRNA encoding calcitonin, calcitonin gene related peptide and proopiomelanocortin in human tumors. 348 30


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