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

Proximal tubule cells were isolated from swine kidney and cultured for periods of more than 30 days. The cells formed confluent monolayers after plating on a collagen surface and they were passaged more than 5 times on this matrix. The cells maintain several metabolic functions of proximal tubule cells, including gluconeogenesis and the ability to respond to epinephrine and parathyroid hormone. Gluconeogenesis, a principal metabolic pathway in proximal tubule cells, was examined as a function of days in culture. The isolated cells showed a nearly constant rate of gluconeogenesis from 14C-lactate, 14C-alanine and 14C-glycerol with no significant loss of activity for at least 30 days in culture. Likewise, the activities of several cytosolic and membrane associated enzymes including, alkaline phosphatase, delta-glutamyltransferase, fructose-1,6-bisphosphatase and phosphofructokinase were nearly constant over the same time period. The cells responded to treatment with epinephrine and parathyroid hormone, and the rate of gluconeogenesis from 14C-lactate doubled in the presence of these hormones. The morphological and biochemical evidence obtained in these studies show that the proximal tubule cells isolated from swine kidney provide an excellent well defined system for studying the hormonal regulation of carbohydrate metabolism in this tissue.
Mol Cell Biochem 1989 Jun 01
PMID:Regulation of gluconeogenesis in swine kidney proximal tubule cells. 277 Jul 16

The nonselective alpha-adrenergic agonist oxymetazoline inhibits parathyroid hormone (PTH)-stimulated cAMP production in intact OK cells, an epithelial cell line derived from an American opossum kidney. This inhibition, however, is not blocked by alpha 2-adrenergic receptor antagonists. After excluding several alternate hypotheses to explain this anomalous activity of oxymetazoline, we hypothesized that oxymetazoline activates a receptor in OK cells that is negatively coupled to adenylate cyclase but distinct from the alpha 2-adrenergic receptor. Prior exposure of OK cells to pertussis toxin blocks the inhibitory response to oxymetazoline, suggesting involvement of a guanine nucleotide-binding regulatory protein. Screening various compounds for attenuation of PTH-stimulated adenylate cyclase showed that serotonin (5HT) is a potent and fully efficacious agonist. Desensitization of alpha 2-receptor-mediated inhibition of cAMP production by epinephrine did not alter the response to either 5HT or oxymetazoline, indicating that these compounds do not produce their effect by activating alpha 2-adrenergic receptors. The 5HT1 receptor-selective antagonist methiothepin, but not ketanserin (5HT2-selective) or ICS-205,930 (5HT3-selective), blocked the response to both 5HT and oxymetazoline. The potency of methiothepin for antagonizing oxymetazoline-induced inhibition of PTH-stimulated cAMP production was not significantly different from its potency for the 5HT-induced effect. These data indicate that OK cells express a 5HT1 receptor that is negatively coupled to adenylate cyclase and that oxymetazoline is an agonist at these receptors.
Mol Pharmacol 1988 Jul
PMID:Oxymetazoline inhibits adenylate cyclase by activation of serotonin-1 receptors in the OK cell, an established renal epithelial cell line. 283 61

We reported recently the presence of somatostatin-like immunoreactivity (SLI) in the glomerulus of rat kidney. In the present study, we examined factors affecting SLI release from isolated rat glomeruli using a perifusion system. Perifusate containing a mixture of essential amino acids stimulated SLI release, while other hormonal agents such as parathyroid hormone, vasopressin, angiotensin II, bradykinin, epinephrine, PGE2, known to have direct actions on the glomerulus, had no discernible effect on SLI release. Addition of somatostatin to the perifusate did not affect either basal or angiotensin II-stimulated PGE2 release from isolated glomeruli. Our preliminary results demonstrate the stimulatory effect of mixed amino acids on somatostatin release from isolated glomeruli. Further studies are needed to elucidate the possible physiological significance of the present findings.
Mol Cell Endocrinol 1985 Jul
PMID:Amino acids release somatostatin-like immunoreactivity from isolated rat glomeruli. 286 84

The responsiveness of parathyroid cells in insulin deficient and short-term diabetic rats was investigated by morphometric analysis. Insulin deficiency was produced by intravenous injection of D-mannoheptulose and short-term (7 days) diabetes mellitus by intraperitoneal application of streptozotocin. Parathyroid glands were stimulated for parathyroid hormone secretion by decreasing the serum calcium concentration through intravenous infusion of EGTA. Parathyroid cells of controls, insulin deficient, and short-term diabetic rats responded to reduced serum calcium by a 45% increase of the cell surface area. This increase is assumed to be the result of the membrane-bound transport of parathyroid hormone from the Golgi complex and secretory granules to the plasma membrane and subsequent exocytic release of parathyroid hormone induced by the low serum calcium concentration. Therefore, the unimpaired increase in the cell surface area of parathyroid cells in insulin deficient and short-term diabetic rats indicates that insulin does not modulate the release of parathyroid hormone. It is also considered likely that synthesis of parathyroid hormone is not suppressed in short-term diabetes but that fat metabolism is disturbed leading to accumulation of lipid vacuoles.
Virchows Arch B Cell Pathol Incl Mol Pathol 1988
PMID:Unimpaired membrane dynamics in parathyroid cells in insulin deficient rats. 289 31

In order to suppress the parathyroid glands by inducing hypercalcemia, young rats were fed a diet containing a low (0.02%) phosphate content. After 28 days blood samples were taken for estimation of serum calcium, phosphate and immunoreactive parathyroid hormone levels. Both parathyroids from each animal were subjected to serial sectioning so that the total glandular volume could be calculated by light microscopy. Volume and surface densities of cells and organelles were measured according to conventional stereological principles, so that the total volumes and surface areas could be estimated. Phosphate depletion caused marked growth retardation. The animals also developed hypophosphatemia, but in spite of pronounced hypercalcemia the levels of circulating immunoreactive parathyroid hormone remained unchanged. The volume of the parathyroids was reduced, but only to an extent commensurate with the reduced body mass. In the experimental group the volume density of cells was unchanged, but that of nuclei was increased; the volume density of Golgi complexes was reduced. The densities of the other cell components measured, namely the volume density of mitochondria and the surface densities of secretory cells, nuclear membranes and rough endoplasmic reticulum were unchanged. When the volumes and surfaces were expressed in absolute terms and related to total body mass, no differences between the groups were apparent.(ABSTRACT TRUNCATED AT 250 WORDS)
Virchows Arch B Cell Pathol Incl Mol Pathol 1988
PMID:Stereological studies of the parathyroids in the young rat with hypercalcemia induced by severe phosphate depletion. 290 Nov 63

A protein which specifically binds the amino terminal domain of parathyroid hormone (PTH) on nitrocellulose blots of polyacrylamide gels was fragmented with cyanogen bromide (CNBr), and two fragments were sequenced through 20 residues. The sequence obtained was 100% homologous with the beta-subunit of bovine F1 mitochondrial ATPase. Purified F1 ATPase from bovine heart and Escherichia coli were obtained and the binding of PTH examined on the blots. The beta-subunit of the bovine enzyme bound PTH specifically through its amino terminal domain. However, both the alpha- and beta-subunit of the E. coli enzyme were found to bind the hormone. This binding was also specific for the amino terminal domain of the hormone. The subcellular distribution of the PTH-binding protein from bovine kidney was also examined further. While the mitochondria and plasma membrane appear to possess similar PTH-binding capability, submitochondrial particles enriched in F1 ATPase were also enriched in PTH-binding activity.
Mol Cell Endocrinol 1988 Sep
PMID:The beta-subunit of the bovine mitochondrial F1 ATPase specifically binds the amino terminal domain of parathyroid hormone. 290 85

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

Both retinoids and the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibit expression of the differentiated phenotype by rabbit costal chondrocytes in culture, as judged by morphological changes and decreased sulfation of glycosaminoglycans (GAG). However, the inhibition of the differentiated phenotype of chondrocytes in TPA-treated cells is restored by parathyroid hormone (PTH), while the inhibition by retinoids is not [Takigawa et al. (1982) Mol. Cell. Biochem. 42, 145-153; Takigawa et al. (1983) Cell Differ. 13, 283-291]. In the present study, we examined the difference between TPA-treated chondrocytes and retinoic acid-treated chondrocytes to determine the mechanism of the restoration of the differentiated phenotype in de-differentiated cells treated with TPA. PTH increased the activity of ornithine decarboxylase [ODC; EC 4.1.1.17], a rate limiting enzyme of polyamine biosynthesis, and proteoglycan synthesis in chondrocytes pretreated with TPA as well as in normal chondrocytes. The maximal stimulations of ODC activity and GAG synthesis were observed 4 h and 24-36 h, respectively, after addition of PTH. The dose-response curve for ODC induction by PTH was parallel to that of PTH-stimulated proteoglycan synthesis both in TPA-treated chondrocytes and in normal chondrocytes. PTH also increased the intracellular cyclic AMP level after 2 min in TPA-treated cells as in normal cells. Addition of dibutyryl cyclic AMP (DBcAMP) induced ODC and restored proteoglycan synthesis in TPA-treated cells. The dose-response curve for induction of ODC by DBcAMP was parallel to that of DBcAMP-stimulated proteoglycan synthesis in both TPA-treated chondrocytes and normal chondrocytes. On the other hand, the increases by PTH in the intracellular cyclic AMP level, ODC activity, and proteoglycan synthesis were inhibited in chondrocytes pretreated with a combination of TPA and retinoic acid as well as in those pretreated with retinoic acid alone. TPA stimulated the syntheses of DNA and RNA in chondrocytes but did not increase the cyclic AMP level or ODC activity. PTH and DBcAMP inhibited the syntheses of DNA and RNA both in TPA-treated cells and in normal cells. These results suggest that ODC induction mediated by elevation of cyclic AMP plays an important role in re-differentiation of de-differentiated cells pretreated with these agents.
 ...
PMID:Comparison of inhibition by a tumor promoter (12-O-tetradecanoylphorbol-13-acetate) of expression of the differentiated phenotype of chondrocytes in rabbit costal chondrocytes in culture with inhibition by retinoic acid. 300 24

Receptor binding assays demonstrate that bovine parathyroid hormone (PTH) and human PTH(1-34) can displace [125I]iodoglucagon from binding to its receptor in rat liver plasma membranes. The displacement of [125I]iodoglucagon requires several thousand-fold more bovine PTH or human PTH(1-34) than glucagon. However, the PTH peptides are more effective than secretin, which up to a concentration of 10(-5) M exhibits no ability to displace [125I]iodoglucagon. The greater potency of PTH compared with secretin occurs despite the fact that secretin shows a great deal of sequence homology with glucagon while PTH shows none. We demonstrate by circular dichroism that in the presence of 3 mM SDS glucagon and hPTH(1-34) have similar secondary structure contents, while secretin is more helical. Our results suggest that receptors can recognize gross conformational features of a peptide hormone in addition to interacting with a specific amino acid sequence. The ability of PTH to interact with glucagon receptors can be modulated by incorporation of charged amphiphiles into the plasma membrane. Negatively charged taurodeoxycholic acid increases the binding of the more cationic PTH while positively charged myristyltrimethylammonium bromide decreases this interaction. These effects demonstrate that receptor specificity can be modulated by its lipid environment and that electrostatic interactions between the hormone and the membrane surface can contribute to receptor binding.
Mol Cell Endocrinol 1987 Feb
PMID:Conformational determinants in receptor recognition of peptide hormones: interaction of parathyroid hormone with the glucagon receptor. 303 Aug 52

The effects of the Ca2+ ionophore A23187 on parathyroid hormone (PTH) secretion and cytoplasmic free Ca2+ concentration (Ca2+i) were measured at different extracellular Ca2+ concentrations using dispersed cells from patients with hyperparathyroidism (HPT). The addition of a low concentration of the Ca2+ ionophore to quin2-loaded cell preparations resulted in the apparent normalization of calcium-regulated Ca2+i. At all extracellular calcium concentrations Ca2+i reached significantly higher values in the presence of the ionophore and the dose-response relationship was shifted to the left. Under similar conditions calcium-regulated PTH release was correspondingly corrected with an increased suppressibility and left-shifted dose-response relationship. The data render strong support for a disturbed regulation of Ca2+i as a major factor in the pathophysiology of HPT.
Mol Cell Endocrinol 1986 May
PMID:Normalizing effect of Ca2+ ionophore on cytoplasmic Ca2+ and parathyroid hormone release of dispersed parathyroid cells from patients with hyperparathyroidism. 308 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>