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)

OPC-18790 [(+/-)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]- 2(1H)-quinolinone], a novel positive inotropic agent, was investigated in several in vitro and in vivo experiments to elucidate its cardiovascular effects and its mechanism of action. In isolated blood-perfused dog heart preparations, OPC-18790 increased contractile force at 10 to 1,000 nmol i.a.; increased coronary arterial blood flow at 30 to 1,000 nmol; and decreased sinus rate slightly at 1,000 nmol. Atrio-ventricular nodal conduction was slightly facilitated with OPC-18790 (10 to 1,000 nmol), whereas ventricular automaticity tended to decrease. OPC-18790 (10(-6) to 10(-4) M) increased contractile force in isolated ventricular muscles of dogs, cats, rabbits and guinea pigs but not rats. OPC-18790 increased left ventricular contractile force dose-dependently in anesthetized open-chest dogs and in conscious dogs with slight or no changes in heart rate and blood pressure. The positive inotropic effect of OPC-18790 was not affected by beta-blockade. OPC-18790 (10(-5) to 10(-4) M) prolonged the duration of action potential in guinea pig papillary muscles. Na+, K(+)-ATPase was not inhibited, but peak-III phosphodiesterase (low Km cyclic AMP specific fraction, inhibited by cyclic GMP) was inhibited by OPC-18790 (IC50 = 0.41 x 10(-6) M) in dog myocardium. However, such an inhibitory action of phosphodiesterase can hardly be reconciled with the lack of a positive chronotropic effect shown by OPC-18790. Thus, these results suggest that OPC-18790 may have an additional mechanism. The cardiovascular effects revealed by this study suggest that OPC-18790 may exert a beneficial effect in the treatment of congestive heart failure.
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PMID:Cardiovascular actions of OPC-18790: a novel positive inotropic agent with little chronotropic action. 132 45

We used postembedding electron microscopic immunocytochemistry with colloidal gold to determine the ultrastructural distribution of Na+,K(+)-ATPase in the sciatic and optic nerves of the rat. Using a polyclonal antiserum raised against the denatured catalytic subunit of brain Na+,K(+)-ATPase, we found immunoreactivity along the internodal axolemma of myelinated fibers in both nerves. This antiserum did not produce labeling of nodal axolemma. These results suggest that an important site of energy-dependent sodium-potassium exchange is along the internodal axolemma of myelinated fibers in the mammalian CNS and PNS and that there may be differences between the internodal and nodal forms of the enzyme.
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PMID:Immunocytochemical demonstration of Na+,K(+)-ATPase in internodal axolemma of myelinated fibers of rat sciatic and optic nerves. 164 59

Aldose reductase was visualized by light and electron microscopy using a goat anti-rat antibody with immunoperoxidase and immunogold, respectively. Ouabain-sensitive, K(+)-dependent, p-nitro-phenylphosphatase, a component of (Na+, K+)-ATPase, was localized at the electron microscopic level by enzyme histochemistry using p-nitro-phenylphosphate as substrate. In peripheral nerve, spinal ganglia and roots, the Schwann cell of myelinated fibers was the principal site of aldose reductase localization. Immunostaining was intense in the paranodal region and the Schmidt-Lanterman clefts as well as in cytoplasm of the terminal expansions of paranodal myelin lamellae and the nodal microvilli. Schwann cell cytoplasm of unmyelinated fibers were faintly labelled. Endoneurial vessel endothelia, pericytes and perineurium failed to bind appreciable amounts of aldose reductase antibody. However, mast cell granules bound antibody strongly. In contrast, p-nitro-phenylphosphatase reaction product was detected in the nodal axolemma, terminal loops of Schwann cell cytoplasm and the innermost layer of perineurial cells. In endothelial cells, reaction product was localized on either the luminal or abluminal, or on both luminal and abluminal plasmalemma. Endothelial vesicular profiles were often loaded with reaction product. Occasional staining of myelin and axonal organelles was noted. Mast cells lacked reaction product.
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PMID:Fine-structural localization of aldose reductase and ouabain-sensitive, K(+)-dependent p-nitro-phenylphosphatase in rat peripheral nerve. 165 Jan 13

We have recently observed increase in Type I fibres in mouse soleus--but not extensor digitorum longus--muscles as a result of repeated muscle damage induced by voluntary wheel running. The most likely mechanism underlying the changes in fibre type composition is a redistribution of motor units with axonal sprouting and formation of new synapses. To test this hypothesis we exercised mice on a motor-driven treadmill once (3 x 3 h with 30 min rest periods in between, 14 m min-1, slope 6 degrees) or repeatedly (8-10 times at intervals of 3-5 days) and quantified axonal sprouting after staining with zinc iodide-osmium. In the contralateral solei, muscle damage and fibre type changes were evaluated with standard histochemical techniques. Significant numbers of damaged muscle fibers were found 0-15 days after a single exercise as compared to unexercised control animals (range 0.0-0.3% of the fibres in sedentary, n = 5, vs 2.1-14.8% in exercised muscles, n = 10) and repeated damage occurred in repeatedly exercised animals. In muscles of sedentary animals 3.8 +/- 1.4% SD of the examined endplates (n = 880, 5 muscles) had nodal or terminal sprouts. The incidence of sprouting was significantly elevated 3-21 days after a single exercise (7.5 +/- 1.8%, n = 2855, 12 muscles, P less than 0.01 signed-rank test), and more so after repeated running (12.0 +/- 2.5%, n = 1505, 6 muscles, P less than 0.01). Fibre type distributions were not different from controls 3 weeks after a single running episode, but after the 6-7 weeks of repeated running a significant increase in undifferentiated fibres at the cost of Type II fibres was found (9.7 +/- 3.4% versus 1.0 +/- 0.5% in sedentary controls, P less than 0.05, t-test); undifferentiated fibres express both Type I and Type II myofibrillar ATPase and are considered as fibres in the process of changing their types. These observations strongly support the assumption that sprouting and formation of new synapses--followed by motor unit enlargement and redistribution--occur as a result of muscle damage.
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PMID:Axonal sprouting and changes in fibre types after running-induced muscle damage. 172 41

There is no published description of the distribution of free Ca2+, nor of the distribution of Ca(2+)-ATPase activity associated with the maintenance of low axoplasmic Ca2+ concentrations, in normal central myelinated nerve fibres. We have used the oxalate-pyroantimonate technique to localise free Ca2+, together with the lead-citrate technique to localise Ca(2+)-ATPase activity within myelinated fibres from the adult guinea-pig optic nerve. Pyroantimonate precipitate occurred within the axoplasm at nodes of Ranvier and the internode, at areas of myelin disruption, within Schmidt-Lanterman incisures (SLI) and glial paranodal loops. But precipitate was absent from the axoplasm beneath SLI and at the paranode. Ca(2+)-ATPase activity was localised in axonal smooth endoplasmic reticulum (SER), the outer membrane of mitochondria, the nodal axolemma, the glial membranes of the paranodal loops, the SLI and the external aspect of the myelin sheath. We have demonstrated large domains within the axons of CNS fibres where calcium is present or absent. Moreover, we have shown that, where calcium is absent, there is localisation of Ca(2+)-ATPase activity, which would serve to remove calcium from the adjacent axoplasm. Our results are compared with information obtained from PNS fibres and some differences of distribution discussed.
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PMID:Localisation of calcium ions and calcium-ATPase activity within myelinated nerve fibres of the adult guinea-pig optic nerve. 183 65

Acute reversible diabetic nerve dysfunction has been associated with a reversible myo-inositol-related (Na+ + K+)-ATPase defect, while poorly reversible chronic nerve dysfunction correlates with progressive axoglial dysjunction of peripheral nerve. The causal relationships between biochemical and neuroanatomical abnormalities and those of nodal membrane function are not known. Nodal clamp examinations were carried out in the sciatic nerve of diabetic BB-rats to elucidate the events underlying diabetic nerve dysfunctions and how these relate to metabolic and structural defects of diabetic nerve. With increasing duration of diabetes, there was a progressive decline in nodal action potentials attributable to decreased Na+ permeability and a decrease in the membranous Na+ gradient. Vigorous insulin therapy in short-term (6-week) diabetic BB-rats normalized the Na+-permeability defect and the membranous Na+ gradient. These defects did not reverse in long-term (24-week) diabetic animals subjected to the same treatment. This poorly reversible nodal dysfunction accounts for the not readily reversible conduction defect in chronic diabetes and is probably directly related to irreversible axoglial dysjunction.
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PMID:Reversible and irreversible nodal dysfunction in diabetic neuropathy. 243 93

Ca++-ATPase plays an important role in regulation of the intracellular Ca++ concentration. Biochemical studies of brain have demonstrated that Ca++-ATPase co-purifies with synaptosomes, with synaptic plasma membrane and synaptic vesicle fractions. To better understand the role of this enzyme in normal brain function, we used an electron microscopic (EM) cytochemical method to determine the localization of Ca++-ATPase in rat brain. Reaction product occurred along cytoplasmic membranes. Specific areas of increased reaction product were seen at many but not all post-synaptic densities. Intracellular Ca++-ATPase reaction product was associated with all synaptic vesicles examined and with the Golgi and smooth endoplasmic reticulum (SER). Unlike the situation in peripheral nerve, Ca++-ATPase at the node of Ranvier in the CNS localized preferentially to the nodal axolemma. The localization of Ca++-ATPase at synaptic vesicles agrees with the biochemical evidence for its localization and with the cytochemical evidence for Ca++-ATPase sequestration in those vesicles. The restricted localization at postsynaptic densities suggests that it may be involved in extrusion of Ca++ at synapses where neurotransmitter release causes Ca++ influx.
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PMID:Ca++-ATPase in the central nervous system: an EM cytochemical study. 252 42

The chronic complications of diabetes are thought to be caused by an interaction between hyperglycemia, or other metabolic consequences of insulin deficiency, and independent genetic or environmental factors that are poorly defined. Several potentially relevant biochemical sequelae to hyperglycemia have been identified in tissue susceptible to diabetic complications. Among these, a rise in tissue sorbitol secondary to concentration-dependent activation of polyol pathway activity by glucose, and an accompanying fall in tissue myo-inositol and Na-K-ATPase activity have recently been linked to a self-reinforcing cyclic metabolic defect that accounts for rapidly reversible slowing of conduction in peripheral nerve in diabetes. Impaired Na-K-ATPase activity also appears to be responsible for intracellular Na+ accumulation and resultant localized axonal paranodal swelling that characterizes diabetic neuropathy in both humans and laboratory animals. These swellings are thought to be responsible for the subsequent disruption of the nodal apparatus (axo-glial disjunction) and some component of the loss of large and small myelinated fibers. Recent studies have suggested that microvascular insufficiency may also contribute to diabetic neuropathy, especially in non-insulin-dependent diabetes. Aldose reductase activity is concentrated in endoneurial vessels, and similar biochemical mechanisms (ie, sorbitol accumulation, myo-inositol deficiency, and impaired Na-K-ATPase activity) are thought to be operative in the endoneurial microvessels in diabetes. Administration of an aldose reductase inhibitor to patients with diabetic neuropathy is associated with repair of damaged nerve fibers and the appearance of newly generated fibers, presumably secondary to metabolic correction within the nerve fibers themselves or their supporting microvasculature.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The pathogenesis and prevention of diabetic neuropathy and nephropathy. 282 23

The contractile properties of cardiac muscle cells are determined by the molecular composition of the contractile apparatus and in particular by the structure of myosin. Three isoforms of myosin heavy chains have been recently identified in the mammalian heart: alpha and beta myosin heavy chains, present in atrial and ventricular myocardium, and nodal myosin heavy chain, present in sino-atrial and atrio-ventricular nodes. The alpha and beta isoforms are coded by two distinct genes whose expression is tissue and developmental stage-specific, and can be regulated by hormonal and mechanical factors. The relative concentration of the two isoforms is correlated with the maximal velocity of shortening and with the energy cost of force generation. In hyperthyroid myocardium the predominant isoform is the alpha, high ATPase myosin heavy chain and the contraction is fast but less economical; in hypothyroid and in mechanically overloaded myocardium the beta, low ATPase isoform is predominant and the contraction is slower and more economical.
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PMID:[Cardiac myosins and myocardial contraction]. 294 27

This report describes the development and characterization of a battery of highly specific antibodies to sodium/potassium (Na+ + K+)-ATPase and their use in localizing this enzyme in nervous tissue. The immunolabeling characteristics of polyclonal antibodies and monoclonal antibodies (Schenk, D. B., and H. L. Leffert (1983) Proc. Natl. Acad. Sci. U. S. A. 80: 5281-5285) raised against rat renal (Na+ + K+)-ATPase were compared. The interspecies cross-reactivity of the polyclonal anti-rat antibodies was examined by determining their binding to purified rat, eel, or dog enzyme. The immunostaining characteristics of the IgG fraction of the polyclonal antibody preparations, their affinity-purified derivatives, and the monoclonal antibodies were compared. The results obtained with each of these were similar, providing information about where focal concentrations of the enzyme exist within nervous tissue. The IgG fraction of the polyclonal antibody preparations provided the most sensitive probe, facilitating localization of the (Na+ + K+)-ATPase in the tissue sections from various regions of the nervous system. (Na+ + K+)-ATPase-like immunoreactivity was observed along the plasmalemma of alpha-motor neurons and at the nodal axolemma of myelinated axons from the central or peripheral nervous system. It was determined that the absence of labeling for the enzyme along the paranodal or internodal regions of the axolemma was not an artifact due to a limited accessibility of antibody to these regions. Some central nervous system glial cells demonstrated abundant amounts of plasmalemmal and intracellular (Na+ + K+)-ATPase-like immunoreactivity. These cells were identified as astroglia by positive labeling of cells in serial sections for glial fibrillary acid protein immunoreactivity in the soma and radial processes in optic nerve, or velous processes in the cerebellum. Astrocyte processes overlying the nodal axolemma also stained positively for the enzyme. (Na+ + K+)-ATPase-like immunoreactivity was not observed in association with oligodendroglia cell bodies or their processes forming myelin sheaths. In contrast, the plasmalemma of myelinating Schwann cells showed greatest immunoreactivity in the region of the node of Ranvier. Although a focal concentration of immunoreactivity was observed along node- and paranode-associated regions of Schwann cells, a lower level of uniform staining was noted along the entire Schwann cell surface membrane.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Localization of sodium/potassium adenosine triphosphatase in multiple cell types of the murine nervous system with antibodies raised against the enzyme from kidney. 299 2


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