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)

The catalytic alpha-subunit of rat hepatic (Na+, K+)-ATPase (EC 3.6.1.3) has been isolated by immunoaffinity chromatography from microsomes solubilized in n-dodecyl octaethylene glycol monoether. The procedure employs an anticatalytic mouse monoclonal antibody ("9-A5") covalently linked to Sepharose 4B that specifically blocks phosphorylation of the sodium pump's alpha-subunit from [gamma-32P]ATP [Schenk, D. B., Hubert, J.J., & Leffert, H.L. (1984) J. Biol. Chem. 259, 14941-14951]. The hepatic subunit is virtually identical with purified rat, dog, and human renal alpha-subunits as judged by its apparent molecular weight after polyacrylamide gel electrophoresis in sodium dodecyl sulfate (Mr 92K) and its two-dimensional tryptic and chymotryptic peptide maps on cellulose-coated thin-layer plates. In contrast, the structures of authentic renal beta-subunits from the three species differ significantly from each other as judged by their peptide maps; no detectable homologies are seen between their chymotryptic maps and those of putative hepatic "beta"-subunits (Mr 50K and 55K) eluted from 9-A5-Sepharose. Additional studies of ouabain-sensitive 86Rb+ uptake in primary cultures of adult rat hepatocytes reveal inhibition curves with single inflection points (ID50 = 0.1 mM ouabain) in the absence or presence of pump-stimulating peptides like insulin, glucagon, and epidermal growth factor. These findings indicate that rat hepatocytes express only one of two known structurally conserved forms of catalytic subunit (the renallike alpha form) and, if at all, structurally divergent forms of the sodium pump's beta-subunit. In addition, immunoaffinity chromatography with 9-A5-Sepharose facilitates the isolation of (Na+, K+)-ATPases from nonrenal tissues with low levels of sodium pumps.
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PMID:Rat hepatic (Na+, K+)-ATPase: alpha-subunit isolation by immunoaffinity chromatography and structural analysis by peptide mapping. 301 14

The binding characteristics of human epidermal growth factor (EGF) were compared between highly purified canalicular (CMV) and sinusoidal (basolateral) rat liver plasma membrane (SMV) preparations. The dissociation constants (2-3 nM) for these membranes were comparable, while the binding capacity for CMV was approximately half that for SMV. The binding capacity for CMV was too high to be accounted for only by the contamination with sinusoidal membranes, since the measurements of specific activities of various enzymes (Na+,K+-ATPase, alkaline phosphatase, and leucine aminopeptidase) indicated that the extents of the cross contamination with other membrane fractions were at most 10%. Although the physiological function of specific binding of EGF to bile canalicular membrane domain remains to be determined, it may have a role in biliary excretion of EGF. The specific binding of EGF to bile canalicular membranes from rat liver was identified for the first time.
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PMID:Comparison of specific binding of human epidermal growth factor (EGF) to sinusoidal and bile canalicular membranes isolated from rat liver. 326 May 89

Long-term effects of nicotine on cultured cells derived from defined segments of the nephron were studied in vitro. Nicotine was added during a 10-day incubation period to a defined nephron culture medium (NCM) which had been supplemented with one of the following: fetal calf serum (FCS), dexamethasone (D), aldosterone (A), or epidermal growth factor (EGF). Thymidine incorporation (10(-15) mmol/10(3) cells) into cultured cells of the cortical thick ascending loop of Henle (TAL) and of the cortical collecting tubule (CT) was inhibited by nicotine (5 X 10(1) ng/ml) when incubated in NCM only; the presence of FCS or of D (10(-8) M) or of D and EGF (25 ng/ml) prevented this inhibitory effect. Nicotine at a concentration of 5 X 10(2) ng/ml was inhibitory in TAL and CT even in the presence of FCS. Na-K-ATPase activity (pmol/10(3) cells X min-1) was stimulated significantly by D when compared with NCM; nicotine (5 X 10(2) ng/ml) prevented this inductive effect. Transepithelial voltage was 27.1 +/- 6 (mV) after incubation with A (10(-9) M), and 7.2 +/- 4.1 when incubated with A and nicotine (5 X 10(2) ng/ml). These data indicate that nicotine may interfere with factors stimulating cell proliferation, sodium pump enzyme activity, and ion flux (voltage). An effect of nicotine on the cellular Na-entry step would be consistent with the data.
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PMID:Effects of nicotine on epithelial nephron cells in culture. 609 Jul 65

Na+/H+ exchange is stimulated in a variety of cell types by addition of mitogenic polypeptides such as epidermal growth factor or platelet-derived growth factor. In order to assess the importance of Na+/H+ exchange in the mitogenic response, it is desirable to have available inhibitors of this process which exhibit high affinity and good specificity. We characterize in this report a number of 5-alkylamino-substituted derivatives of amiloride [3,5-diamino-6-chloro-N-(diaminomethylene)pyrazinecarboxamide++ +] which show much higher affinity than the parent compound for the Na+/H+ antiporter in A431 cells. High affinity is conferred by substitution with two alkyl groups and is increased by introducing a branched alkyl chain. An analogue bearing a 5-anilino group is also very potent. These analogues effectively inhibit the elevation of intracellular pH upon stimulation of Na+/H+ exchange by growth factors. We have assessed other potential inhibitory effects of these compounds on cellular metabolism. In agreement with previous reports, we find that amiloride inhibits protein synthesis both in cells and in cell-free translation systems. While amiloride and its analogues show similar inhibition of protein synthesis in a cell-free system, most analogues inhibit cellular protein synthesis at much lower concentrations than does amiloride. These analogues are also potent inhibitors of purified Na,K-ATPase and cause a profound decrease in intracellular K+ as well as ATP content. These latter effects, however, require analogue concentrations which are 5-7 times higher than those inhibiting cellular protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of potent Na+/H+ exchange inhibitors from the amiloride series in A431 cells. 609 47

The behaviour of Na+/K+ ATPase during cell growth has been studied. Enzymatic activity, which is slightly affected during normal growth, is strongly reduced if the cells are incubated with epidermal growth factor (EGF). Evidence indicates that there is a double mechanism of action of the hormone.
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PMID:Na+/K+ ATPase and cell growth: EGF modulates enzymatic activity in cultured fibroblasts. 613 Aug 96

Depletion of intracellular potassium (K+) caused a marked reduction in the rate of endocytosis of receptor-bound low density lipoprotein (LDL) and epidermal growth factor (EGF) in human fibroblasts. K+ could be depleted slowly by a 3-hr incubation of cells in isotonic K+-free buffer. Rapid K+ depletion was induced by incubation of cells for 5 min with hypotonic medium, followed by transfer to isotonic K+-free buffer. Within 30 min of this treatment, cellular K+ levels fell by more than 60%. When the K+ level fell below a threshold of 40% of normal, the number of coated pits declined by 80% and the rate of endocytosis of 125I-LDL decreased by 70 to 95% despite normal to increased receptor binding. Similar results were obtained with 125I-epidermal growth factor. Addition of KCl to the culture medium up to 2 hr after K+ depletion restored cellular K+ levels and returned endocytosis of 125I-LDL promptly to normal. RbCl was as effective as KCl, but CsCl, LiCl, and (CH3)4NCl had no effect. Restoration by KCl was blocked by ouabain, indicating that uptake via the Na+/K+ ATPase was required. These data demonstrate that depletion of intracellular K+ reversibly arrests coated pit formation and receptor-mediated endocytosis in human fibroblasts.
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PMID:Depletion of intracellular potassium arrests coated pit formation and receptor-mediated endocytosis in fibroblasts. 614 96

Thyroid hormones modulate energy metabolism and importantly influence growth and development. These effects are independently mediated. Thyroid calorigenesis is influenced predominantly via nuclear receptor mediated synthesis of mitochondrial respiratory assemblies and cell membrane sodium potassium ATPase. Accumulating evidence suggests that many of the thyroid hormone effects on development are mediated via growth factors, including somatomedins (SM), erythropoietin (EP), nerve growth factor (NGF) and epidermal growth factor (EGF). Thyroid hormone binding to nuclear receptors is known to stimulate growth hormone (GH) synthesis, and thyroid hormones probably potentiate GH stimulation of SM production as well as the anabolic effects of SM. The production of EP, NGF and EGF also are thyroid hormone responsive, and it seems likely that these growth factors mediate the thyroid hormone effects on erythrocyte production, autonomic and perhaps central nervous system maturation, and epidermal development, respectively.
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PMID:The thyroid hormone effects on growth and development may be mediated by growth factors. 621 63

A great deal of knowledge has been gained concerning the activation of adenylate and guanylate cyclase in epidermal cells. Adenylate cyclase is activated by 4 different independent receptors-responding respectively to catecholamine (beta), to prostaglandins (E), to histamine (H2), and to adenosine and it phosphorylated derivatives. Upon activation, each of these receptors becomes unresponsive to further stimulation by its specific stimulator. Guanylate cyclase, on the other hand, is activated by histamine (H1) and epidermal growth factor (EGF). Unlike EGF, the histamine activation is extremely rapid (less than 5 minutes). Epidermal cells are permeable (leak) to cyclic GMP but not cyclic AMP. When the skin is traumatized or injured in any way (even by intradermal injection) there is a sudden catastrophic change in the intracellular levels of the cyclic nucleotides (and of ATP). Cyclic AMP rapidly rises to perhaps 5-10 times its normal resting level while cyclic GMP falls to 10-20% of its level in vivo. The rise in cyclic AMP is due to activation of adenylate cyclase while the fall in cyclic GMP is due in major part to activation of cyclic GMP phosphodiesterase (and perhaps the fall in ATP is due to activation of ATPase). The changes in ATP and cyclic AMP can be reversed by incubating the tissue in a buffered salt solution containing glucose, but this does not normalize the cyclic GMP content. The fall in cyclic GMP can be prevented by a phosphodiesterase inhibitor (IBMX ). This series of events has been called the "ischemia effect." However, it implies that a lack of oxygen is at fault, and that has not been shown to be the case. Its underlying cause and possible physiologic significance are not known. Do these changes in cyclic nucleotides have effects on epidermal proliferation? And does EGF? Agents which increase cyclic AMP do inhibit the epidermal outgrowth and mitotic activity of explant cultures of pig skin. Cyclic GMP does increase outgrowth at a particular concentration. Histamine, which elevates both cyclic nucleotides, has a biphasic action depending on its concentration. These findings imply that these nucleotides do act as one of the controls of epidermal proliferation. The action of cyclic GMP is not accompanied by detectably increased phosphorylation of epidermal proteins. On the other hand, EGF action which also enhances epidermal outgrowth is characterized by an increased protein phosphorylation that precedes any increase in cellular cyclic GMP. We conclude that the action of EGF is independent of the cyclic nucleotide system.
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PMID:Cyclic GMP system in the epidermis. 626 50

Cyanogen bromide-cleaved epidermal growth factor (CNBr-EGF) binds to EGF receptors with reduced affinity compared to the native hormone but fails to induce DNA synthesis. However, at similar receptor occupancy, CNBr-EGF is as potent as EGF in activating early cell responses to the hormone. The phosphorylation of membrane proteins, the stimulation of Na+-K+-ATPase as reflected by the ouabain-sensitive uptake of 86Rb of fibroblasts, changes in the organization of microfilaments and in cell-morphology, and the activation of the enzyme ornithine-decarboxylase are all induced by CNBr-EGF as well as EGF Our results are consistent with the notion that EGF-induced phosphorylation could act as a "second messenger" for the action of various EGF-induced responses such as activation of Na+-K+-ATPase, changes in the cytoskeleton and cell morphology, and the activation of the enzyme ornithine decarboxylase. However, the stimulation of phosphorylation of membrane proteins and other early responses are either not required or necessary but insufficient for the induction of DNA synthesis. Suboptimal concentrations of EGF together with CNBr-EGF stimulate DNA synthesis in human fibroblasts. Other growth factors such as insulin, fibroblast growth factor, and prostaglandin F2 alpha, which potentiate the mitogenic response of EGF, do not effect the response to CNBr-EGF. This suggests that the restoration of the mitogenic properties of CNBr-EGF by suboptimal doses of EGF occurs at the level of EGF receptors or during their processing.
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PMID:A nonmitogenic analogue of epidermal growth factor induces early responses mediated by epidermal growth factor. 628 91

Defined cultures of rabbit kidney cortical collecting tubule (CCT) and cortical thick ascending limb of Henle's loop (CAL) were grown in monolayers from individual microdissected tubules and maintained for up to five passages, a maximum of 53 days. CCT cells contained cytochemically demonstrable vasopressin-stimulated adenylate cyclase, whereas CAL cells were characterized by the localization of Na+-K+-ATPase. [3H]thymidine labeling index decreased with time in primary cultures in the presence or absence of 3% serum. When added to unsupplemented serum-free media alone or in combinations, the growth factors dexamethasone, thyroxine, insulin, epidermal growth factor, and prolactin stimulated [3H]thymidine incorporation to different extents. CCT cells were maximally stimulated by addition of dexamethasone alone, whereas a combination of dexamethasone, thyroxine, insulin, and prolactin was most stimulatory for CAL cells. Addition of hormones concerned with renal ion and water transport to fully supplemented serum-free media inhibited [3H]thymidine labeling index: 1) vasopressin, isoproterenol, and dibutyryl cAMP were equally inhibitory in CCT and CAL cultures; 2) parathyroid hormone and prostaglandin E1 were more inhibitory in CAL cultures; and 3) aldosterone was particularly inhibitory in CCT cultures.
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PMID:Differential response to hormones of defined distal nephron epithelia in culture. 629 9


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