Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human polycystic kidney disease (PKD) epithelia were successfully grown in culture and expressed abnormal characteristics. Cysts lining epithelia of superficial and deep cysts were microdissected and compared to individual normal human proximal straight tubules (PST) and cortical collecting tubules (CCT) grown in defined media. PKD cyst epithelia differed from normal renal tubular epithelia in growth patterns and structural and functional properties. PKD epithelia grew more rapidly and showed cyst-like areas in otherwise confluent monolayers. Polygonal and elongate cells contained an epithelial-specific cytokeratin antigen and had polarized morphology. An extremely abnormal basement membrane morphology was seen and consisted of some banded collagen and numerous unique blebs or spheroids. These blebs were apparently extruded from intracellular vacuoles and stained with ruthenium red, suggesting a proteoglycan component. Cytochemistry of marker enzymes demonstrated the presence of NaK-ATPase and alkaline phosphatase, but a lack of gamma-glutamyl transpeptidase. The response of adenylate cyclase activity to vasopressin, parathyroid hormone, and forskolin was significantly diminished in PKD cells as compared to PST and CCT. These studies suggest a defect in cell growth and basement membrane synthesis in human PKD. Cultured PKD epithelia provide a new tool for the study of the pathogenesis of this disease.
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PMID:A new method for studying human polycystic kidney disease epithelia in culture. 243 Nov 89

Regulation of the acidity of osteoclasts was determined in situ on the endocranial surfaces of mouse calvaria using acridine orange, a fluorescent weak base. Osteoclasts could be identified by large size, multiple nuclei, relatively small numbers of cells, and the way and the extent to which they took up the dye. Nonosteoclastic cells were stained mainly in their nuclei and occasionally in a few lysosomes surrounding their nuclei, which were uniformly single in nonosteoclasts. Nuclei in osteoclasts were also stained, but the staining of the nuclei was partially masked by the intensity and completeness of the staining of the cytoplasm. In some cells the cytoplasmic staining appeared to be in discrete granules, giving the cytoplasm a bright, frothy appearance. This fluorescence was present in both treated and untreated cells and aided in identifying the osteoclasts. Acridine orange fluorescence at 624 nm intensity, and hence, osteoclast acidity, was increased by parathyroid hormone and prostaglandin E2. Parathyroid hormone-induced increases in acidity were inhibited by calcitonin, cortisol, sodium fluoride, and prostaglandin E2. Furthermore, osteoclast acidity was dependent largely or partially on maintenance of K+ and Na+ gradients, patent Na+ channels, chloride-bicarbonate exchange, and H+, K+-ATPase. These findings demonstrate that osteoclasts become acidified by mechanisms similar to those occurring in gastric parietal cells.
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PMID:Humoral and ionic regulation of osteoclast acidity. 243 48

Several studies suggested that catecholamines modulate renal sodium and water excretion by direct stimulation of adrenergic receptors located on the renal proximal tubule. However, neither the mechanism nor the class of adrenoceptor involved in this effect have yet been established definitively. In the present study, we examined the effects of L-norepinephrine (NE) and selective alpha-1, alpha-2 and beta adrenergic agonists on monovalent cation transport and on Na+-K+-adenosine triphosphatase (ATPase) activity from homogenates, intact tubules and highly purified basolateral membranes prepared from superficial rabbit kidney cortex. Our results showed that neither NE nor specific alpha-1, alpha-2 and beta adrenergic agonists (10 microM) modified ouabain-sensitive uptake of 86Rb+ (a K+ analog) in intact proximal tubules. Similarly, it is demonstrated that NE and alpha and beta adrenergic agonists did not affect Na+-K+-ATPase activity from homogenates, intact tubules and basolateral membranes. The integrity of the alpha-2 adrenergic receptor system, the predominant adrenergic subtype in rabbit proximal tubule, was supported by the following findings: 1) maximal binding of [3H] rauwolscine was about 4-fold higher in basolateral membranes than in homogenates; 2) 5'-guanylimidodiphosphate induced a 27-fold increase in the Ki of NE for alpha-2 receptor in basolateral membranes; 3) NE (5 microM) inhibited by 35% parathyroid hormone-stimulated cyclic AMP production in intact tubules. In conclusion, these data fail to demonstrate that NE, as well as other adrenergic agonists, directly increases Na+-K+-ATPase in the rabbit proximal tubule. Further investigations are needed to clarify the interaction of catecholamines with the renal Na+K+ pump.
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PMID:Adrenergic agonists and the Na+-K+-adenosine triphosphatase from rabbit proximal tubules and their basolateral membranes. 254 43

Abnormalities in the function of the central nervous system exist in chronic renal failure (CRF) and some of these derangements may be related to excess parathyroid hormone (PTH) which causes a rise in brain calcium. The latter may affect metabolism of neurotransmitters such as norepinephrine (NE) in brain synaptosomes. We measured NE content, uptake and release in brain synaptosomes of CRF rats and studied whether excess PTH affects these parameters. Synaptosomes from rats with 21 days of CRF compared to those from normal animals have higher calcium content (11.4 +/- 0.92 vs. 7.1 +/- 0.50 nmol/mg protein, P less than 0.01) and lower Na-K ATPase activity (6.5 +/- 0.81 vs. 11.4 +/- 0.76 mumol Pi/mg protein/hr, P less than 0.01). NE content (11.0 +/- 0.60 vs. 13.6 +/- 0.55 pmol/mg protein/hr, P less than 0.01), uptake (46 +/- 4.5 vs. 110 +/- 5.9 pmol/mg protein times 50 min, P less than 0.01) and release (2.0 +/- 0.2 vs. 5.1 +/- 0.47 pmol/mg protein times 10 min, P less than 0.01). Parathyroidectomy (PTX) in CRF rats kept normocalcemic reversed these abnormalities in brain synaptosomes; indeed calcium content, Na-K ATPase activity and NE content, uptake and release in synaptosomes from PTX-CRF rats were not different from those seen in normal rats.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Abnormal norepinephrine uptake and release in brain synaptosomes in chronic renal failure. 255 7

Gentamicin nephrotoxicity increases renal cortex calcium and sodium and decreases renal cortex Na-K-ATPase activity. Human acute renal failure is accompanied by an increase in parathyroid hormone (PTH), a hormone that stimulates calcium uptake by tissues, and by a decrease in thyroid hormone, a hormone that increases renal cortex Na-K-ATPase activity. This study evaluated the role of extracellular calcium, PTH, and thyroxine in the pathogenesis of gentamicin nephrotoxicity. Chronically parathyroidectomized hypocalcemic rats (PTXG) given gentamicin (30 mg/kg s.c. twice daily for 8 days) were not protected from renal failure when compared with intact rats given gentamicin (NG), serum creatinine being 4.4 +/- 1.0 and 3.7 +/- 0.7 mg/dl, respectively, compared with normals (N), 1.2 +/- 0.1 mg/dl. Rats given thyroxine (10 micrograms/100 g body wt for 10 days) before and during gentamicin (PTXT4G) had a serum creatinine not significantly different from normals, 2.1 +/- 0.4 mg/dl. Plasma T4 was reduced in PTXG, NG, and PTXT4G compared with N, but the value for PTXT4G was significantly higher than for either PTXG or NG. Renal cortex Na-K-ATPase activity (mumol Pi X mg prot-1 X h-1) was lower in PTXG (2.3 +/- 0.2) and NG (2.4 +/- 0.5) compared with N (3.7 +/- 0.1), but activity was not reduced in PTXT4G (3.2 +/- 0.2) Thyroxine was protective also against gentamicin nephrotoxicity in intact rats. Clearance and excretion studies indicated that this protection did not result from an increase in glomerular filtration rate, filtered load of calcium, or urinary calcium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effect of thyroxine but not parathyroidectomy on gentamicin nephrotoxicity. 257 82

In a recent study in acutely parathyroidectomized, fasted rats, infused with parathyroid hormone (PTH), superimposition of euglycemic hyperinsulinemia within the physiologic range completely reversed the decline in tubular reabsorption of Pi (TRPi) induced by PTH. As an extension of these observations on insulin as a counterregulator of Pi homeostatis, the present results demonstrated that similar insulin administration prevented a decrease in TRPi when PTH infusion was superimposed. This was, moreover, observed in the fed state and at doses of insulin which did not stimulate renal cortical Na-K-ATPase activity. Subsequent studies addressed the role of insulin in a PTH-independent phosphaturic state, namely that induced by Pi loading. Under such conditions and while the resultant hypocalcemia of hyperphosphatemia was circumvented by the addition of calcium to the infusate, insulin substantially increased the renal tubular reabsorptive capacity for Pi, thereby demonstrating an antiphosphaturic action of insulin independent of PTH. Furthermore, when increased filtered loads of Pi and PTH administration were combined during insulin infusion, TRPi was greater than when PTH was administered alone during similar insulin infusion. When calcium infusion did not accompany Pi loading with a resultant fall in serum calcium, euglycemic hyperinsulinemia did not affect TRPi, indicating abolition of the antiphosphaturic action of insulin by hypocalcemia.
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PMID:Effects of physiologic hyperinsulinemia on renal phosphate handling in the rat: a role for calcium. 269 27

Studies were made on the mechanism of the effect of parathyroid hormone (PTH) on the activity of (Ca2++Mg2+)-ATPase, a membrane bound Ca2+-extrusion pump enzyme from the basolateral membranes (BLM) of canine kidney (Km for free Ca2+ = 1.3 X 10(-7) M, Vmax = 200 nmol Pi/mg/min). At 1 X 10(-7) M free Ca2+, both PTH (10(-7)-10(-6) M) and cAMP (10(-6)-10(-4) M) stimulated (Ca2++Mg2+)-ATPase activity dose-dependent and their stimulatory effects were inhibited completely by 5 microM H-8, an inhibitor of cAMP-dependent protein kinase. PTH (10(-7) M) also caused 40% increase in 32P incorporation into the BLM and 5 microM H-8 inhibited this increase too. PTH (10(-7) M) was found to stimulate phosphorylation of a protein of Mr 9000 by cAMP dependent protein kinase and 5 microM H-8 was found to block this stimulation also. From these results, it is proposed that PTH stimulates (Ca2++Mg2+)-ATPase activity by enhancing its affinity for free Ca2+ via cAMP-dependent phosphorylation of a BLM protein of Mr 9000.
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PMID:Increase of (Ca2++Mg2+)-ATPase activity of renal basolateral membrane by parathyroid hormone via cyclic AMP-dependent membrane phosphorylation. 282 70

The role of dietary salt and calcium on changes in cellular cation metabolism has been evaluated in 11 salt-sensitive hypertensive black adults maintained on the following four metabolic diets for 56 days, 14 days on each diet in a repeated measures format: 356 mg Ca-1000 mg sodium (NA); 356 mg Ca-4000 mg Na; 934 Ca-1000 mg Na; and 934 mg Ca-4000 mg Na. Increasing dietary Na at the lower Ca intake caused significant (P less than 0.05) increases in parathyroid hormone (PTH) and 24-hour cyclic AMP excretion that were associated with significant (P less than 0.01) increases in erythrocyte intracellular calcium (from 5.4 +/- 0.7 to 11.1 +/- 3.7 microM), Ca-ATPase (from 37.2 +/- 2.4 to 42.2 +/- 2.1 pmol/min/10(6) cells) and intracellular sodium (from 220.5 +/- 7.4 to 262.0 +/- 8.3 micrograms/mL) and decreases (P less than 0.05) in Na/K-ATPase (from 1.90 +/- 0.55 to 1.48 +/- 0.47 pmol/min/10(6) cells) and intracellular magnesium (Mg) (from 52.4 +/- 3.5 to 43.8 +/- 2.4 micrograms/mL). Adding calcium to this high sodium diet reversed these effects, whereas adding calcium to the low sodium diet was without significant effect. These results indicate that dietary salt causes increases in intracellular sodium and calcium and that the antihypertensive effect of dietary calcium in salt-sensitive individuals may be attributable in part to preventing this salt-induced elevation in intracellular calcium. This increase in intracellular calcium could be due to the observed increase in PTH levels or to the salt-induced reduction in intracellular magnesium that appears to suppress Na/K-ATPase and thereby increases intracellular sodium.
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PMID:Erythrocyte cation metabolism in salt-sensitive hypertensive blacks as affected by dietary sodium and calcium. 285 Aug 20

The relationship between changes in the pressor response to infused noradrenaline induced by intravenous injection of ouabain, an Na+,K+-ATPase inhibitor, and plasma renin activity and plasma ionized calcium was examined in 16 normotensive subjects and in 16 patients with essential hypertension. These patients were divided into 11 normal-renin and five low-renin essential hypertensives. The pressor response was significantly greater in low-renin hypertensives than in normotensives and normal-renin hypertensives. Following the injection of ouabain, the pressor response was significantly increased with no change in basal levels of blood pressure, plasma noradrenaline concentration, plasma calcium and plasma parathyroid hormone in both normotensives and essential hypertensives. The pressor response to noradrenaline was negatively correlated with levels of plasma noradrenaline and calcium after the injection of ouabain as well as before the injection in normotensives and essential hypertensives. The regression line between the pressor response and that of plasma noradrenaline or plasma calcium was significantly shifted towards a higher pressor response in normotensives, but not in essential hypertensives. The changes in the pressor response to noradrenaline induced by the injection of ouabain was significantly smaller in essential hypertensives, particularly in low-renin hypertensives, compared with normotensives. These results suggest that: (1) ouabain increases the pressor response to noradrenaline; (2) this increase is related to calcium metabolism; (3) endogenous Na+,K+-ATPase inhibitor(s) might be elevated in essential hypertensives; and (4) an increase in endogenous Na+,K+-ATPase inhibitor might, therefore contribute to an enhanced noradrenaline response in essential hypertensives, particularly in low-renin hypertensives.
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PMID:The effect of ouabain on pressor responses to infused noradrenaline in patients with essential hypertension. 285 44

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.
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PMID:The beta-subunit of the bovine mitochondrial F1 ATPase specifically binds the amino terminal domain of parathyroid hormone. 290 85


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