Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the past 5 years, we have identified idiopathic hypercalciuria in five of seven patients referred for evaluation of renal glycosuria between 1985 and 1991. The children, all boys, ranged in age from 6 to 12 years. Endocrine function was normal, and none of the patients had hyperparathyroidism, hypercalcemia, renal tubular acidosis, or other secondary causes of hypercalciuria. The calcium/creatinine ratio in a fasting urine specimen was elevated in all five children who had hypercalciuria, with a mean value (+/- SD) of 0.34 +/- 0.06 (normal, < 0.2). In one child who had renal colic with spontaneous passage of gravel-like material, the idiopathic hypercalciuria persisted after 1 week on a diet containing 2000 mg of sodium and 300 mg of calcium. On the basis of studies that examined the site along the nephron responsible for hypercalciuria in rats with streptozocin-induced diabetes, we speculate that in children with renal glycosuria, there is defective reabsorption of glucose and calcium in the straight portion of the proximal tubule or in the collecting duct. It is likely that a similar mechanism accounts for the idiopathic hypercalciuria in children with diabetes mellitus.
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PMID:Hypercalciuria in children with renal glycosuria: evidence of dual renal tubular reabsorptive defects. 841 May 29

In order to investigate the pathogenesis of medullary nephrocalcinosis, rabbit inner medullary collecting duct cells were grown in media containing different Ca++, PTH and pH levels. It was found that high Ca++ (7.8mM) only reduced growth slightly and that crystalline deposits were found under the cells. This suggests that high Ca++ is not severely toxic to the cells but can lead to deposition of calcium beneath the basement membrane. PTH did not effect cell growth even in the presence of high Ca++ implying that it has an indirect effect on tubular cells in medullary nephrocalcinosis associated with hyperparathyroidism. In renal tubular acidosis these cells are subjected to a persistently high urinary pH and low interstitial pH. Raising the pH reduced the cell growth in normal Ca++ medium whereas lowering the pH increased cell growth in vitro. Our results show that nephrocalcinosis is not due to the direct effect of raised pericellular Ca++ or PTH alone and that persistently alkaline tubular fluid may play a role.
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PMID:An in vitro model of nephrocalcinosis using rabbit inner medullary collecting tubular cell culture. 273 Jun 43

While many studies have demonstrated a nephrogenic diabetes insipidus syndrome (NDI) with prolonged lithium (Li) treatment, experiments in the isolated rat papillary collecting duct have suggested that the defect may be due to a circulating factor that inhibits the action of arginine vasopressin (AVP). Since Li-treatment can produce a form of hyperparathyroidism and parathyroid hormone (PTH) can act as a partial agonist to AVP, in vivo and in vitro studies were performed on rats made polyuric by daily intraperitoneal (i.p.) Li (4 mmol/kg) treatment. Li-treatment for three weeks produced an increase in PTH (194 +/- 20 compared with 118 +/- 18 pg/ml in control rats; P < 0.01) as well as an increase in the plasma calcium concentration (2.38 +/- 0.05 compared with 2.25 +/- 0.04 mmol/liter; P < 0.05). Clearance studies were performed on water loaded Li-treated and control rats, and the defect in urine concentration was only observed with a low physiological concentration of AVP (10 mU/kg body wt over 5 min). Maximal urine osmolality was 328 +/- 31 compared with 613 +/- 81 mOsm/kg (P < 0.05) in controls. There was no detectable difference with a prolonged maximal physiological AVP concentration (10 mU bolus and 50 mU/kg body wt per hr) and papillary solute concentrations were unchanged. When Li-treated rats had been parathyroidectomized (PTX), a significant difference in urine concentration with the low AVP concentration could not be demonstrated when compared to non-PTX control rats. In the isolated papillary collecting duct preparation a medium was used that contained fresh plasma from Li-treated or control rats, both intact and PTX. Experiments using plasma from Li-treated intact rats produced only a 25.4 +/- 5.1% increase in diffusional water permeability with the addition of AVP (200 microU/ml) compared to 52.6 +/- 9.0% in control rats (P < 0.01). However, when plasma from Li-treated PTX rats was used, the AVP induced increase in water permeability (54.7 +/- 11.2%) was not significantly different from that observed in PTX control rats. These studies show that the NDI-like defect in Li-treatment is small and easily overcome by higher concentrations of AVP and suggests that the concentration defect is at least in part due to increased circulating levels of PTH acting as a partial agonist to AVP and thereby inhibiting its hydroosmotic action.
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PMID:Mechanism of lithium-induced polyuria in the rat. 884 Feb 63

The recent cloning of a G-protein-coupled, extracellular calcium [(Ca2+)e]-sensing receptor (CaRG) from the parathyroid, kidney and brain of several species has clarified the molecular mechanisms underlying Ca2+-sensing by parathyroid and other cell types. It has long been suspected that such a receptor existed on parathyroid cells, coupled to intracellular second messengers through guanine nucleotide regulatory (G) protein which is able to recognize and respond to (Ca2+)e. Recently, functional screening of a cDNA library constructed from bovine parathyroid mRNA led to the isolation of a 5.3-kb clone expressing maximal Ca2+-stimulated Cl- currents in oocytes. This 5.3-kb cDNA encodes a protein of 1,085 amino acids with three principal predicted structural domains. The CaRG protein is present in chief parathyroid cells, in C cells of the thyroid, in the cortical thick ascending limb (TAL) and collecting duct of the kidney, and in discrete brain areas. CaRG may play several physiological roles. It is a central element in the control of both parathyroid and calcitonin secretion by (Ca2+)e. Moreover, functional evidence for its participation in the regulation of renal Ca2+ reabsorption in TAL and water reabsorption in the collecting duct has been obtained. Mutations of the CaRG gene are responsible for hereditary and familial parathyroid disorders, and a decrease in CaRG expression has been documented in primary and secondary uremic hyperparathyroidism. The expression of CaRG in several additional organs and tissues allows speculation on the potential involvement in other pathologies.
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PMID:The calcium receptor in health and disease. 963 31

The ability of parathyroid cells to recognize and respond to (i.e., "sense") small changes in the extracellular Ca2+ concentration (Ca2+o) plays a crucial role in mineral ion homeostasis. Expression cloning in Xenopus laevis oocytes enabled isolation of a cDNA coding for the bovine parathyroid CaR. CaRs were later isolated from human parathyroid and kidney, rat kidney, brain and C-cell, rabbit kidney, and chicken parathyroid. All are tissue and species homologs of the same ancestral gene. The predicted CaR protein has a large extracellular amino-terminus, which binds polycationic CaR agonists; a central core with seven membrane-spanning helices, documenting that it is a G protein-coupled receptor; and an approximately 200 amino acid carboxyl-terminal tail. The CaR is highly expressed in parathyroid and C-cells, along almost the entire nephron and gastrointestinal (GI) tract and within numerous regions of the brain, particularly hippocampus, cerebellum, and hypothalamus. The CaR's physiological importance has been documented by the identification of hyper- and hypocalcemic syndromes due to inactivating or activating CaR mutations, respectively. Familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT) are caused by loss-of-function CaR mutations producing Ca2+o "resistance," while autosomal dominant hypocalcemia is the result of activating mutations rendering CaRs overly sensitive to Ca2+o. In addition to showing altered parathyroid responsiveness to Ca2+o, patients with FHH reabsorb too much urinary Ca2+ and Mg2+ at a given Ca2+o, while those with autosomal dominant hypocalcemia excrete too much, illustrating the CaR's key role in renal handling of divalent cations. Recent in vitro data suggest that the CaR directly regulates renal water handling in the collecting duct. Indeed, patients with FHH concentrate their urine normally, despite their hypercalcemia, while those with autosomal dominant hypocalcemia can exhibit impaired urinary concentration at normal or even low Ca2+o, suggesting that the CaR enables coordination of renal calcium and water handling. In addition to serving these "homeostatic" roles, the CaR likely also enables Ca2+o to serve additional roles as an extracellular messenger. The receptor regulates key Ca2+ and K(+)-permeable ion channels in hippocampal and other brain cells and likely senses local changes in Ca2+o within the brain microenvironment accompanying neuronal activation. It is also present in and regulates ion channels in lens epithelial cells, potentially playing some role in cataract development in hypoparathyroid patients. In keratinocytes and epithelial cells of the gastrointestinal tract, in contrast, the CaR may regulate cellular proliferation and differentiation, processes known to be modulated by Ca2+o in these cell types. Thus, in addition to sensing and regulating systemic Ca2+o, the CaR likely enables Ca2+o to act as a local signal for cells within specific microenvironments, such as the brain or eye.
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PMID:The calcium-sensing receptor (CaR) permits Ca2+ to function as a versatile extracellular first messenger. 976 11

Renal and metabolic adverse effects of lithium therapy are illustrated by the case report of a manic depressive woman aged 78 years, so treated for about 25 years. Long term lithium therapy with plasma lithium level in the therapeutic range impairs renal concentrating ability in 25-50% of the patients (when the total ingested amount reaches 100-200 mol, 700-1400 g). About 10-15% of the patients have overt nephrogenic diabetes insipidus (NDI) with elevated antidiuretic hormone plasma level and unresponsiveness to desmopressin. In rats, lithium treatment down regulates expression of the main water channel, aquaporin 2, in the renal collecting duct. NDI may be complicated by hypernatremic dehydration if the access to water is restricted, whatever the cause. Treatment of NID is best started with nonsteroidal antiinflammatory drugs, being then substituted for amiloride. Prolonged lithium therapy may induce chronic interstitial nephritis. In some patients this may result in mild or moderate non progressive chronic renal insufficiency. Acute lithium intoxication (with supratherapeutic doses) may be complicated by acute renal failure (ARF); even in the absence of ARF hemodialysis is indicated when plasma lithium level reaches 4 mmol/l or more. Other metabolic adverse effects of lithium therapy include: hypercalcemia due to hyperparathyroidism (in 5-10% of the patients); hypothyroidism (often latent); hyperthyroidism. In conclusion, these renal and metabolic adverse effects are generally mild or moderate, allowing the continuation of lithium therapy in most affected patients.
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PMID:[Renal and metabolic complications of lithium]. 1079 6

Inactivation of the transcription factor AP-2 beta in a genetically mixed C57BL/6/129S1 mouse strain resulted in perinatal lethality as a consequence of massively enhanced apoptotic death of renal epithelial cells (Genes Dev 1997;11:1938-1948). Recently, we observed that the phenotype is modulated by genetic background because AP-2 beta mutant mice, backcrossed onto 129P2 background, survive approximately 2 weeks after birth, allowing for a detailed analysis of kidney function. Here we show that kidneys reveal varying amounts of cysts derived from all tubular structures (proximal and distal tubuli, collecting ducts). However, all mice died irrespective of the degree of cyst formation. Serum analysis of AP-2 beta mutant animals revealed defective tubular secretory function and ion homeostasis including severe hypocalcemia, hyperphosphatemia, and hyperuremia. Because hormonal calcium regulation was not impaired, the mice developed secondary renal hyperparathyroidism as typically observed in patients with terminal renal failure. We further demonstrate that molecular defects in the collecting duct system lead to insufficient water retention and urinary concentration. In summary, our studies reveal essential, nonredundant roles of AP-2 beta in renal tubular functions.
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PMID:Terminal renal failure in mice lacking transcription factor AP-2 beta. 1269 60

Vitamin D receptor (VDR) modulators are used to treat hyperparathyroidism secondary to chronic kidney disease (CKD). The therapy is associated with reduced mortality in stage 5 CKD patients, who experience an extremely high cardiovascular disease (CVD)-related mortality rate. Chen et al. report that VDR is involved in regulating type A natriuretic peptide receptor (NPR-A) in inner medullary collecting duct cells. The regulation of NPR-A may be one of several mechanisms by which VDR activation reduces CVD risk in CKD.
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PMID:Vitamin D receptor: a highly versatile nuclear receptor. 1744 Apr 94

Lithium-induced nephrogenic diabetes insipidus (NDI) is a rare and difficult-to-treat condition. We describe the case of an 81-year-old woman with bipolar treated with lithium and no previous history of diabetes insipidus. She was hospitalized due to disturbance of consciousness and was diagnosed with, hypercalcemia, hyperparathyroidism, and NDI. Parathyroidectomy was contraindicated and parathyroid hormone level was improved insufficiently after cinacalcet initiation, percutaneous ethanol injection therapy was performed for the enlarged parathyroid gland. After improvement in hypercalcemia and unsuccessful indapamide treatment, triamterene was administrated to control polyuria. Lithium is one of the indispensable maintenance treatment options for bipolar disorder, but it has the side effect of NDI. Lithium enters the collecting duct's principal cells mainly via the epithelial sodium channel (ENaC) located on their apical membranes, ENaC shows high selectivity for both sodium and lithium, is upregulated by aldosterone, and inhibited by triamterene. To our knowledge, this is the first publication on triamterene use in lithium-induced NDI patients.
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PMID:Triamterene in lithium-induced nephrogenic diabetes insipidus: a case report. 3277 36