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)

A wealth of studies performed with a spectrum of methods spanning simple clearance studies to the molecular identification of ion transporters has increased our understanding of how approximately 1.7 kg of NaCl and 180 L of H2O are absorbed by renal tubules in man and how the urinary excretion is fine-tuned to meet homeostatic requirements. This review will summarize our current understanding. In the proximal nephron, approximately 60 to 70% of the filtered Na+ and H2O is absorbed together with approximately 90% of the filtered HCO3-. The exact quantities are determined by many regulatory factors, such as glomerulotubular balance, angiotensin II, endothelin, sympathetic innervation, parathyroid hormone, dopamine, acid base status and others. The essential components of absorption are luminal membrane Na+/H+ exchange and the basolateral (Na+ + K+)-ATPase. In the thick ascending limb of the loop of Henle, 20 to 30% of the filtered NaCl is absorbed via Na+2Cl-K+ cotransport driven by the basolateral (Na+ + K+)-ATPase. No H2O is absorbed at this nephron site. The transport rate is determined by the Na+ load and by several hormones and neurotransmitters, including prostaglandins, parathyroid hormone, glucagon, calcitonin, arginine vasopressin (AVP), and adrenaline. In the distal tubule, some 5 to 10% of the filtered load is absorbed via Na+Cl- cotransport in the luminal membrane driven by the basolateral (Na+ + K+)-ATPase. The rate of transport is again determined by the delivered load and by several hormones and neurotransmitters. One of the tasks of the collecting duct is to control the absorption of approximately 10 to 15% of the filtered H2O, regulated by AVP, and just a few percent of the filtered Na+, controlled by aldosterone and natriuretic hormone. The water absorption proceeds through the luminal membrane via aquaporin 2 and through the basolateral membrane via aquaporin 3 channels and is driven by the osmotic gradient built up by the counter current concentrating system. The Na+ absorption occurs via Na+ channels present in the luminal membrane driven by the basolateral (Na+ + K+)-ATPase. With no pharmacological interference, urinary excretion of Na+ can vary between less than 0.1% and no more than 3% of the filtered load, and that of H2O can vary between 0.3 and 15%.
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PMID:Physiology of renal sodium transport. 1065 44

Vasodilator responses to anandamide (arachidonylethanolamide) and potassium ions were compared with those mediated by endothelium-derived hyperpolarizing factor (EDHF) in guinea-pig isolated basilar artery contracted with prostaglandin F2alpha. In this artery, EDHF-mediated responses can be evoked by acetylcholine in the presence of both indomethacin (10 microM) and NG-nitro-L-arginine (0.3 mM). In endothelium-denuded arterial segments, which failed to respond to acetylcholine, anandamide was still able to evoke a complete relaxation. Anandamide (10 microM) did not affect the resting membrane potential, whereas acetylcholine (10 microM) hyperpolarized the smooth muscle cells by 23 mV in the presence of indomethacin and NG-nitro-L-arginine. Pre-treatment with capsaicin (10 microM) or resiniferatoxin (0.1 microM) abolished the anandamide-induced relaxation, but had no effect on the EDHF-mediated relaxation induced by acetylcholine. Treatment with a mixture of the calcium-sensitive potassium channel inhibitors, apamin and charybdotoxin, which abolishes EDHF-mediated relaxation in this artery, did not affect the relaxation evoked by anandamide. The additional presence of glibenclamide or ciclazindol, inhibitors of ATP-sensitive and voltage-dependent potassium channels, also had no effect on the anandamide-induced relaxation. Increasing the potassium ion concentration by 2-10 mM induced inconsistent vasodilator responses. However, re-admission of potassium ions to preparations incubated in potassium-free solution elicited almost complete and sustained relaxations. A short incubation period with ouabain (10 microM for 10 min) or cooling (18-22 degrees C) abolished these responses, whereas the acetylcholine-induced relaxation in the presence of indomethacin and NG-nitro-L-arginine was unaffected (ouabain) or partially reduced (cooling). The anandamide-induced relaxation was also abolished by ouabain and cooling. Furthermore, ouabain inhibited the vasodilator response to capsaicin, but not that to calcitonin gene-related peptide (CGRP), and per se evoked a release of CGRP from the artery. The gap junction uncoupler, 18alpha-glycyrrhetinic acid (100 microM), affected neither the EDHF-mediated relaxation induced by acetylcholine nor the vasodilator responses to anandamide and potassium ions. Thus, EDHF-mediated vasorelaxation in the guinea-pig basilar artery does not seem to involve Na+/K+-ATPase, sensory nerves or gap junctions. These results indicate that EDHF is neither anandamide nor potassium ions in this artery.
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PMID:Differential actions of anandamide, potassium ions and endothelium-derived hyperpolarizing factor in guinea-pig basilar artery. 1083 8

Insulin as a vascular hormone, apart from its effect on intermediary metabolism, has been considered to play an important role in cardiovascular regulation and pathophysiology of cardiovascular diseases such as essential hypertension, congestive cardiac failure and atherosclerosis. Insulin induces pressor effects by mechanisms of increased sympathetic activity, renal sodium retention and proliferation of vascular smooth muscle cells. On the other hand, accumulating evidence indicates that insulin decreases vascular resistance and increases organ blood flow especially in skeletal muscle tissue, indicating that insulin is a vasodilator. Several mechanisms underlying insulin-induced vasodilation have been proposed. Insulin enhances calcium efflux from vascular smooth muscle cells by activating the plasma membrane Ca(2+)-ATPase and causes hyperpolarization by stimulating Na+, K(+)-ATPase and sodium/potassium pump. Insulin also stimulates nitric oxide (NO) synthase and increases release of NO from vascular endothelium to cause vasodilation. An increase in cyclic AMP levels is induced by insulin, via activation of insulin receptors, beta-adrenoceptors and calcitonin gene-related peptide receptors. However, main cause of mechanisms mediating the vasodilation remain obscure. Hypertension is associated with insulin resistance and hyperinsulinemia. Insulin resistance may contribute to hypertension by sympathetic overactivity, endothelium dysfunction and decreased vasodilator action of insulin. Therefore, insulin must be considered a vasoactive peptide and more investigations are needed to better understand the full significance of the hemodynamic effect of insulin.
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PMID:[Vascular effects of insulin]. 1087 80

Calbindin-D28k is an intracellular protein with high affinity for calcium. In the kidney, this protein is exclusively localized in the distal tubule and in the proximal part of the collecting ducts. Functionally, calbindin-D28k is supposed to be involved in the regulation of the reabsorption of calcium and possibly magnesium in the distal nephron though the exact regulatory mechanisms are not yet known. Thus, several theories regarding the functional role of calbindin-D28k have been proposed: The carrier theory describes calbindin-D28k as a transport protein which binds calcium and then transports it from the luminal to the basolateralcell membrane. The buffer theory assumes that calbindin-D28k functions by binding calcium ions to prevent intracellular calcium concentrations from reaching toxic levels. The activator theory describes that calbindin-D28k increases the activity of calcium channels or the enzymatic activity of the Ca++-Mg++-ATPase in the luminal membrane and thereby increases the tubular reabsorption of calcium. The renal calbindin-D28k is dependent upon vitamin D. Pharmacological doses of the active vitamin D metabolite 1,25-(OH)2D increases the concentrations of renal calbindin-D28k, whereas the concentration of calbindin-D28k is low in conditions with reduced levels of circulating 1,25-(OH)2D. Likewise, plasma calcium concentrations, uremia and hypertension affect calbindin-D28k expression. However, several studies have rendered probable the effect of additional factors in the regulation of renal calbindin-D28k. The aim of the present dissertation therefore was to examine the regulation of renal calbindin-D28k in a series of physiological and pathophysiological conditions established in vivo in the rat. A possible correlation between hypertension and calbindin-D28k was examined in three models of experimental hypertension: the genetically defined spontaneous hypertensive rat, the salt-sensitive Dahl rat and the renovascular hypertensive rat. These three models clearly demonstrated three separate patterns in the calcium metabolism, but the studies were unable to support a role for calbindin-D28k in the development of hypertension. In all three models the development of hypertension caused an increased plasma 1,25-(OH)2D. This increase was accompanied by either unaltered or reduced levels of renal calbindin-D28k possibly secondary to a cellular resistance against 1,25-(OH)2D. Magnesium binds to calbindin-D28k with a relatively high affinity. The regulation of urinary magnesium excretion takes place in the distal tubule where calbindin-D28k is found in high concentrations. Therefore, a possible relation between magnesium and calbindin-D28k was examined. The studies demonstrated not previously known connections between magnesium intake, urinary magnesium excretion and renal calbindin-D28k which suggests that this protein is involved in the regulation of magnesium homeostasis by the kidney. Calcitonin increases the reabsorption of calcium in the distal tubule. Therefore, the effect ofcalcitonin on renal calbindin-D28k was examined both by eliminating the endogeneous calcitonin production by a selective thyroidectomy followed by an autotransplantation of the parathyroid glands and further by infusion of calcitonin. These studies demonstrated unchanged concentrations of renal calbindin-D28k. It was concluded that the increased calcium reabsorption induced by calcitonin in the distal tubule is not mediated by calbindin-D28k. Urinary calcium excretion is in part regulated by the action of PTH on calcium reabsorption in the distal nephron. Previous reports of increased expression of renal calbindin-D28k in uremic rats led us to suggest that secondary hyperparathyroidism associated with uremia induced the synthesis of renal calbindin-D28k. Therefore, the effect of PTH was examined in a study comprising selective parathyroidectomy and infusions of PTH, PTHrP, 1,25-(OH)2D and calcium. (ABSTRACT TRUNCATED)
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PMID:Regulation of renal calbindin-D28K. 1109 7

Rat collecting ducts exhibit type I or type III K(+)-ATPase activities when animals are fed a normal (NK) or a K(+)-depleted diet (LK). This study aimed at determining functionally the cell origin of these two K(+)-ATPases. For this purpose, we searched for an effect on K(+)-ATPases of hormones that trigger cAMP production in a cell-specific fashion. The effects of 1-deamino-8-D-arginine vasopressin (dD-AVP), calcitonin, and isoproterenol in principal cells, alpha-intercalated cells, and beta-intercalated cells of cortical collecting duct (CCD), respectively, and of dD-AVP and glucagon in principal and alpha-intercalated cells of outer medullary collecting duct (OMCD), respectively, were examined. In CCDs, K(+)-ATPase was stimulated by calcitonin and isoproterenol in NK rats (type I K(+)-ATPase) and by dD-AVP in LK rats (type III K(+)-ATPase). In OMCDs, dD-AVP and glucagon stimulated type III but not type I K(+)-ATPase. These hormone effects were mimicked by the cAMP-permeant analog dibutyryl-cAMP. In conclusion, in NK rats, cAMP stimulates type I K(+)-ATPase activity in alpha- and beta-intercalated CCD cells, whereas in LK rats it stimulates type III K(+)-ATPase in principal cells of both CCD and OMCD and in OMCD intercalated cells.
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PMID:Cellular origin and hormonal regulation of K(+)-ATPase activities sensitive to Sch-28080 in rat collecting duct. 1109 23

The Drosophila melanogaster homologue of an insect calcitonin-like diuretic hormone was identified in a BLAST search of the Drosophila genome database. The predicted 31-residue amidated peptide (D. melanogaster DH31; Drome-DH31) was synthesised and tested for activity on fruit fly Malpighian tubules. It increases tubule secretion by approximately 35 % of the response obtained with a myokinin from the housefly Musca domestica (muscakinin; Musdo-K) and has an EC50 of 4.3 nmol x l(-1). The diuretic activities of Drome-DH31 and Musdo-K were additive when tested at threshold and supra-maximal concentrations, which suggests that they target different transport processes. In support of this, Drome-DH31 increased the rate of secretion by tubules held in bathing fluid with a reduced Cl- concentration, whereas Musdo-K did so only in the presence of Drome-DH31. Stimulation with Drome-DH31 increased the lumen-positive transepithelial potential in the main secretory segment of the tubule. This was attributed to activation of an apical electrogenic proton-translocating V-ATPase in principal cells, since it was associated with hyperpolarisation of the apical membrane potential and acidification of secreted urine by 0.25 pH units. Exogenous 8-bromo-cyclic AMP and cyclic GMP increased tubule secretion to the same extent as Drome-DH31 and, when tested together with the diuretic peptide, their activities were not additive. Stimulation with Drome-DH31 resulted in a dose-dependent increase in cyclic AMP production by tubules incubated in saline containing 0.5 mmol x l(-1) 3-isobutyl-1-methylxanthine, whereas cyclic GMP production was unchanged. Taken together, the data are consistent with Drome-DH31 activating an apical membrane V-ATPase via cyclic AMP. Since the K+ concentration of the secreted urine was unchanged, it is likely that Drome-DH31 has an equal effect on K+ and Na+ entry across the basolateral membrane.
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PMID:The Drosophila melanogaster homologue of an insect calcitonin-like diuretic peptide stimulates V-ATPase activity in fruit fly Malpighian tubules. 1131

The (Na+,K+)-ATPase is a plasma membrane protein complex composed of at least three subunits (alpha,beta,gamma) that couples the exchange of three cytoplasmic Na+ ions with two extracellular K+ ions, to the hydrolysis of one molecule ofATP in most animal cells. The gamma-subunit is a 66 residue membrane protein associated with the active alpha/beta binary complex. It can be considered as an archetype of single transmembrane proteins (type I) which may play a modulatory role upon association with functional membrane partners. This paper highlights similar associations observed with other ATPases such as the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA1/SERCA 2a), but also with Cl- and/or K+ currents, ionic channels (HERG, KCNQ1) and G-protein coupled receptors (adrenomedullin, CGRP and calcitonin) which are of particular interest in the cardiovascular field. Here is reviewed the assessed or suggested regulatory role of a family of small plasma/SR associated membrane proteins including gamma-subunit, phospholemman, Mat 8, KCNE (type 1, 2 and 3), RAMP (type 1, 2 and 3), sarcolipin and phospholamban, mainly found in muscular and vascular tissues. These proteins are critical in controlling important biological processes which derive from specific associations with a binding partner and particular subcellular localizations.
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PMID:The gamma-subunit of (Na+,K+)-ATPase: a representative example of human single transmembrane protein with a key regulatory role. 1135 3

Osteoclasts differentiate from hematopoietic precursors of the monocyte/macrophage lineage to mononuclear preosteoclasts and multinuclear mature osteoclasts. In the present study, we report on the establishment of macrophage like cell lines from mouse bone marrow by coculturing bone marrow cells with mouse chondrocytes. Isolated clones (MLC-6 and MLC-7 cells) expressed fully differentiated osteoclast markers, such as calcitonin receptors, vitronectin receptors, tartrate-resistant acid phosphatase and vacuolar H+ -ATPase, in the absence of osteoclast differentiation factor/osteoprotegerin ligand/RANKL/TRANCE, which was essential for osteoclast differentiation. Most clones also maintained expression of a macrophage-associated protein, namely non-specific esterase. Both MLC-6 and MLC-7 cells released cathepsin K into the culture medium. Both clones resolved dentine slices when cocultured with the osteoblast cell line ST2. The cloned cell lines are considered to be useful tools in the study of osteoclast differentiation.
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PMID:Establishment and characterization of macrophage-like cell lines expressing osteoclast-specific markers. 1144 14

The final step in the maternal-fetal transfer of calcium in the placenta involves transport against a concentration gradient across the syncytiotrophoblast basal plasma membrane (BM). Based on animal studies, it has been proposed that parathyroid hormone-related peptide (PTHrP) plays a major role in maintaining the maternal-fetal concentration gradient of calcium. In this study, we tested the hypothesis that a highly conserved mid-region fragment (38-94) of PTHrP directly affects the ATP-dependent calcium transport across BM isolated from full-term human placentas. PTHrP (38-94) stimulated ATP-dependent calcium transport at a concentration within the physiological range (5 pg/ml) and the effect (10-38% increase) was concentration dependent over the range 5 pg/ml to 5 ng/ml (n=8; P<0.05). In contrast, PTH, PTHrP (1-34), PTHrP (67-86) and calcitonin increased BM calcium transport only at concentrations much higher than physiological. The increased calcium uptake was inhibited by the protein kinase C (PKC) inhibitor chelerythrine (n=6; P<0.05). In addition, PTHrP (38-94) increased inositol trisphosphate (IP(3)) production and PKC phosphorylation in human placental BM (n=12; P<0.05). Our data indicate that PTHrP (38-94) stimulates Ca(2+)ATPase in the human syncytiotrophoblast BM vesicles by activating the IP(3)-DAG-PKC pathway. We suggest that PTHrP (38-94) is important in maintaining the calcium concentration gradient across the placental barrier in the human.
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PMID:Parathyroid hormone-related peptide (38-94) amide stimulates ATP-dependent calcium transport in the Basal plasma membrane of the human syncytiotrophoblast. 1242 49

Although calcitonin is well known to be a potent inhibitor of bone resorption, it remains unknown how it regulates osteoclastic H(+) transport. In this study, we examined the effects of calcitonin on H(+) extrusion in cultured rat resorbing osteoclasts using an intracellular pH (pHi) indicator, BCECF [2'7'-bis-(2-carboxyethyl)- 5-carboxyfluorescein]. Resorbing osteoclasts were identified by their formation of resorbing pits on calcium phosphate-coated quartz coverslips. Both basal pHi and H(+) extrusion activity were significantly higher compared to non-resorbing osteoclasts. Two types of H(+)-extruding systems were identified by pharmacological and immunocytochemical means: a bafilomycin-A(1)-sensitive and an amiloride-sensitive system [H(+) extrusion mediated by a vacuolar type proton pump (V-ATPase) and by a Na(+)/H(+) exchanger (NHE), respectively]. Calcitonin inhibited both H(+) extrusion activities in a dose-dependent manner and this action was mimicked by protein kinase A (PKA) activators, but not by protein kinase C (PKC) activators. Pretreatment with PKA inhibitors completely suppressed calcitonin-induced inhibition, whereas neither PKC inhibitors nor calcium chelators suppressed it. These results indicate that calcitonin inhibits H(+) extrusion generated by V-ATPase and NHE via PKA activation. These inhibitory mechanisms of H(+) transport by calcitonin are important for the regulation of bone resorption.
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PMID:Calcitonin inhibits proton extrusion in resorbing rat osteoclasts via protein kinase A. 1263 84


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