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)

Purinergic nerves supply the gastrointestinal tract of vertebrates, including fish, amphibians, reptiles and birds, as well as mammals. Their cell bodies are located in Auerbach's plexus and their axons extend in an anal direction before innervating mainly the circular muscle coat. In the stomach they are controlled by preganglionic cholinergic fibres of parasympathetic origin. They are involved in "receptive relaxation" of the stomach, "descending inhibition" in peristalsis and reflex relaxation of oesophageal and internal anal sphincters. The terminal varicosities of purinergic nerves are characterised by a predominance of "large opaque vesicles," which can be distinguished from the "large granular vesicles" found in small numbers in both adrenergic and cholinergic nerves. Stimulation of purinergic nerves with single pulses produces hyperpolarisations of up to 25 mV (inhibitory junction potentials) in smooth muscle cells. These potentials are unaffected by atropine, adrenergic neuron blocking agents or sympathetic denervation, but are abolished by tetrodotoxin. The "rebound contraction" which characteristically follows cessation of purinergic nerve stimulation is probably due to prostaglandin. Evidence that ATP is the transmitter released from purinergic nerves includes: (1) synthesis and storage of ATP in nerves; (2) release of ATP from the nerves when they are stimulated; (3) exogenously applied ATP mimicking the action of nerve-released transmitter, both producing a specific increase in K+ conductance; (4) the presence of Mg-activated ATPase, 5'-nucleotidase and adenosine deaminase, enzymes which inactivate ATP; (5) drugs (including quinidine, some 2-substituted imidazolines, 2-2'pyridylisatogen and dipyridamole) which produce similar blocking or potentiating effects on the response to exogenously applied ATP and nerve stimulation. Speculations are made about the evolution and development of the nervous system, including the possibility that purinergic nerves are a primitive nerve type.
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PMID:Comparative studies of purinergic nerves. 17 88

We describe a mother and two daughters who had the following clinical manifestations: bluish discoloration of the vermillion ridge of the lips, nipple areolae, and nail beds; discrete telangiectasia of the chest, elbows, and dorsa of the hands; varicosities of the lower part of the legs; and (in the two daughters) migraine headaches. Routine histologic examination of tissue from the lips and elbows disclosed extensive, dilated, horizontal subpapillary telangiectases. Enzyme histochemical stains demonstrated activity of adenosine triphosphatase and leucine aminopeptidase around these dilated vessels. Alkaline phosphatase activity was strikingly absent from the dilated subpapillary vessels. By electron microscopy, these vessels were demonstrated to be postcapillary venules. We propose an autosomal dominant mode of inheritance.
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PMID:Hereditary acrolabial telangiectasia. A report of familial blue lips, nails, and nipples. 43 75

Liquor contacting peptidergic neurons (LCPNs) in the preoptic nucleus of the Japanese eel (Anguilla japonica), are investigated submacroscopically, light microscopically, electron microscopically (transmission and scanning) and histochemically. LCPNs appear in 8--13 per cent of all neurons constituting the preoptic nucleus and their cytoplasm contains many secretory granules stained by aldehyde-thionin or chrome hematoxylin. LCPNs have an epithelial cell-like polarity and their cytoplasmic organella shift to the supranuclear region. LCPNs are classified into three types (A, B, C) according to the liquor contacting portion of the cell: Granular type A neuron (40--50 x 40--50 microns 2), the cell of which is in contact with the cerebrospinal fluid (CSF), is the most common type and distributed in the ventral portion of the preoptic nucleus; this neuron is not connected with the neighboring ependymal cells by tight junctions. Bipolar type B neuron (60 x 30 micron 2), contacts the CSF with the tip of it cell process and is scattered throughout the preoptic nucleus; the cell is connected with the surrounding ependymal cells by tight junction. Bipolar type C neuron (60 x 30 micron 2) possesses a cell process protruded into the third ventricle and is distributed in the dorsal portion of the preoptic nucleus; this also is connected with the adjacent ependymal cells by tight junction. Regardless of type, all LCPNs exhibit a positive acetylcholinesterase and a negative ATPase reaction. Numerous fluorescent varicosities of monoaminergic nerve terminals are closely associated with the cell bodies of the LCPN. LCPNs are likely regulated by monoaminergic fibers.
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PMID:Histological and cytological studies on the liquor contacting peptidergic neurons in the preoptic nucleus of the Japanese eel (Anguilla japonica). 53 83

Endogenous digitalis-like substance (EDLS) is a newly discovered humoral agent which causes sodium-diuresis. EDLS is well known to have inhibitory activity to Na+,K(+)-ATPase and cross-immunoreactivity to digoxin antibody; however, its precise chemical structure has not yet been determined. We had previously developed a histochemical technique for EDLS, i.e., digoxin-immunohistochemistry, and demonstrated that EDLS was produced in the hypothalamic neurons. In the present study, the distribution of EDLS-containing neurons in the hypothalamus of dog and macaque was investigated using this technique, because anti-EDLS antibody cannot be obtained yet. In both species, EDLS neuronal somata were mainly localized in the paraventricular nucleus and the supraoptic nucleus and its accessory nuclei. A number of somata were also scattered in the other hypothalamic areas. The processes of these neurons ran from the area where the somata were located, through the lateral and basal area of the hypothalamus, to the infundibulum. These nerve fibers with varicosities were associated with the primary capillaries of hypophysial portal veins. A few immunopositive nerve fibers were also seen in the pituitary posterior lobe of both species. Intensive immunoreactivities were observed in the subfornical organ and organum vasculosum laminae terminalis. There were no differences between dog and macaque.
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PMID:Distribution of the endogenous digitalis-like substance (EDLS)-containing neurons labeled by digoxin antibody in hypothalamus and three circumventricular organs of dog and macaque. 132 45

1. Mechanisms controlling the secretion of [(3)H]noradrenaline from the noradrenergic nerves of guinea-pig isolated vas deferens, prelabelled by incubation with [(3)H]noradrenaline, were studied using (a) different modes of (extramural or transmural) electrical nerve stimulation (a total of 300 shocks of varying strength, and a duration of 2 msec) at 1-30 Hz, or (b) depolarizing concentrations of K(+) (60-110 mm).2. The fractional rise in efflux of (3)H-labelled material (Deltat) was used to measure the secretion of [(3)H]noradrenaline.3. The dependence of [(3)H]noradrenaline secretion on the external Ca(2+) concentration (1-8 mm) was essentially hyperbolic. Double reciprocal plot analysis (1/Deltat vs. 1/Ca(2+)) of the data yields that blockade of alpha-autoinhibition (phentolamine 1 mum) does not increase the maximal secretory velocity, but does enhance the apparent affinity of the secretory mechanism for external Ca(2+). Exogenous noradrenaline has (qualitatively) opposite effects. The interaction between alpha-autoinhibition and external Ca(2+) thus shows a ;competitive' pattern, indicating that restriction of the utilization of external Ca(2+) is a major mechanism in alpha-autoinhibition of noradrenaline secretion, in this system.4. Phenoxybenzamine (10 mum) and phentolamine (1 mum) increased the secretion of [(3)H]noradrenaline evoked by depolarization with K(+) much less than that caused by electrical nerve stimulation (frequencies up to 10 Hz). Exogenous noradrenaline (1-5 mum) depressed the secretion evoked by both modes of stimulation. The results indicate that alpha-autoinhibition of [(3)H]noradrenaline secretion is mainly operative when the secretory stimulus requires conduction of nerve impulses between varicosities.5. The frequency dependence of [(3)H]noradrenaline secretion was hyperbolic, both in the presence and in the absence of alpha-autoinhibition; at each frequency the secretion (Deltat per shock) increased with the Ca(2+) concentration in the medium (0.6-8 mm). Double reciprocal plot analysis (1/Deltat vs. 1/frequency) of the data yields that the pattern of interaction between external Ca(2+) and facilitation depends on the presence or absence of alpha-autoinhibition (phentolamine 1 mum); in the former case it is ;non-competitive', in the latter ;competitive'. Similar analysis of the effect of facilitation by increasing the length of stimulus trains (from 5 to 300 pulses) at a constant frequency (5 Hz), on the Ca(2+) dependence of Deltat (1/Deltat vs. 1/Ca(2+)) in the absence of alpha-autoinhibition also yields that facilitation promotes utilization of external Ca(2+). These results apparently imply that a rise in external Ca(2+), in the presence of alpha-autoinhibition, augments the secretory response to electrical nerve stimulation mainly by promoting recruitment of active units (varicosities?), without markedly altering their ;affinity' for facilitation. In the absence of autoinhibition (when all units are already recruited?), the results seem to imply that facilitation promotes depolarization-secretion coupling in each, by more efficient utilization of external Ca(2+).6. The pattern of interaction between alpha-autoinhibition and facilitation depends on the Ca(2+)concentration in the medium. At or below the physiological level of Ca(2+) in extracellular fluid (1.2 mm) it is ;non-competitive', indicating that alpha-autoinhibition and facilitation act, at least in part, at separate targets under these conditions. At high (5.4 mm) external Ca(2+) the pattern becomes almost purely ;competitive', indicating that facilitation can, under suitable conditions, overcome all manifestations of alpha-autoinhibition.7. The secretion evoked by electrical nerve stimulation (Deltat per shock, at 1 or 10 Hz) increased with the strength of applied shocks, both when applied extra- or transmurally, in the presence or absence of alpha-autoinhibition. In the former case the rise in (Deltat per shock) vs. (current strength) was hyperbolic, in the latter it followed a biphasic pattern. Double reciprocal plot analysis (1/Deltat vs. 1/current) of the data yields a ;non-competitive' pattern of interaction between facilitation or alpha-autoinhibition, and exogenous current, when stimulation was extramural. When it was transmural the pattern is ;competitive'. The results seem to imply that hyperpolarization, or depolarization, of nerve terminals are major mechanisms whereby alpha-autoinhibition and facilitation, respectively, exert their effects on the secretory response to electrical nerve stimulation.8. Neither activation of Na(+), K(+)-ATPase, nor promotion of G(Cl) appear to be critically involved in alpha-autoinhibition. Experiments with known blockers of G(K) (tetraethylammonium, 4-aminopyridine and Rb(+)) did not give support to the notion that promotion of K(+) efflux is a mechanism whereby prejunctional alpha-adrenoceptors cause (hyperpolarization of nerve terminals and) autoinhibition of secretion. If alpha-autoinhibition does involve K(+) channels in the nerve terminal membrane, then these must be different from the (voltage-sensitive) K(+) channels blocked by the above mentioned inhibitors of K(+) efflux.9. The results are discussed in the context of a model that assumes that local control of noradrenaline secretion from noradrenergic nerves may be exerted both by control of invasion of terminals, and by control of depolarization-secretion coupling in each invaded varicosity. Under suitable conditions facilitation and alpha-autoinhibition may interact at both levels. It proposed that utilization of external Ca(2+) plays a pivotal role for both, and that restriction of invasion of nerve terminal varicosities is the main effect of alpha-autoinhibition, while promotion of depolarization-secretion coupling is the main effect of facilitation, at physiological concentrations of Ca(2+) in the medium. For the nerve the role of this dual control system is proposed to be to ensure ;rotational' activation of varicosities, and for the effector cell of noradrenergic junctions, to increase the signal/noise ratio.
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PMID:Site(s) and ionic basis of alpha-autoinhibition and facilitation of "3H'noradrenaline secretion in guinea-pig vas deferens. 626 64

The time course of most quantal currents recorded with a small diameter electrode placed over visualized varicosities of sympathetic nerve terminals that secrete ATP was determined: these had a time to reach 90% of peak of 1.3-1.8 ms and a time constant of decay of 12-18 ms; they were unaffected by blocking ectoenzymes or the uptake of adenosine. Monte Carlo methods were used to analyze the stochastic interaction between ATP, released in a packet from a varicosity, and the underlying patch of purinoceptors, to reconstitute the time course of the quantal current. This leads to certain restrictions on the possible number of ATP molecules in a quantum (about 1000) and the density of purinoceptors at the junctions (about 1000 microns-1), given the known geometry of the junction and the kinetics of ATP action. The observed quantal current has a relatively small variability (coefficient of variation < 0.1), and this stochastic property is reproduced for a given quantum of ATP. Potentiation effects (of about 12%) occur if two quanta are released from the same varicosity because the receptor patch is not saturated even by the release of two quanta. The simulations show that quantal currents have a characteristically distinct shape for varicosities with different junctional cleft widths (50-200 nm). Finally, incorporation of an ectoenzyme with the known kinetics of ATPase into the junctional cleft allows for a quantal current of the observed time course, provided the number of ATP molecules in a quantum is increased over the number in the absence of the ATPase.
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PMID:Quantal transmission at purinergic junctions: stochastic interaction between ATP and its receptors. 775 56

Considering the mechanisms responsible for age- and Alzheimer's disease (AD)-related neuronal degeneration, little attention was paid to the opposing relationships between the energy-rich phosphates, mainly the availability of the adenosine triphosphate (ATP), and the activity of the glutamic acid decarboxylase (GAD), the rate-limiting enzyme synthesizing the gamma-amino butyric acid (GABA). Here, it is postulated that in all neuronal phenotypes the declining ATP-mediated negative control of GABA synthesis gradually declines and results in age- and AD-related increases of GABA synthesis. The Ca2+-independent carrier-mediated GABA release interferes with Ca2+-dependent exocytotic release of all transmitter-modulators, because the interstitial (ambient) GABA acts on axonal preterminal and terminal varicosities endowed with depolarizing GABA(A)-benzodiazepine receptors; this makes GABA the "executor" of virtually all age- and AD-related neurodegenerative processes. Such a role of GABA is diametrically opposite to that in the perinatal phase, when the carrier-mediated GABA release, acting on GABA(A)/chloride ionophore receptors, positively controls chemotactic migration of neuronal precursor cells, has trophic actions and initiates synaptogenesis, thereby enabling retrograde axonal transport of target produced factors that trigger differentiation of neuronal phenotypes. However, with advancing age, and prematurely in AD, the declining mitochondrial ATP synthesis unleashes GABA synthesis, and its carrier-mediated release blocks Ca2+-dependent exocytotic release of all transmitter-modulators, leading to dystrophy of chronically depolarized axon terminals and block of retrograde transport of target-produced trophins, causing "starvation" and death of neuronal somata. The above scenario is consistent with the following observations: 1) a 10-month daily administration to aging rats of the GABA-chloride ionophore antagonist, pentylenetetrazol, or of the BDZ antagonist, flumazenil (FL), each forestalls the age-related decline in cognitive functions and losses of hippocampal neurons; 2) the brains of aging rats, relative to young animals, and the postmortem brains of AD patients, relative to age-matched controls, show up to two-fold increases in GABA synthesis; 3) the aging humans and those showing symptoms of AD, as well as the aging nonhuman primates and rodents--all show in the forebrain dystrophic axonal varicosities, losses of transmitter vesicles, and swollen mitochondria. These markers, currently regarded as the earliest signs of aging and AD, can be reproduced in vitro cell cultures by 1 microM GABA; the development of these markers can be prevented by substituting Cl- with SO4(2-); 4) the extrasynaptic GABA suppresses the membrane Na+, K+-ATPase and ion pumping, while the resulting depolarization of soma-dendrites relieves the "protective" voltage-dependent Mg2+ control of the N-methyl-D-aspartate (NMDA) channels, thereby enabling Ca2+-dependent persistent toxic actions of the excitatory amino acids (EAA); and 5) in whole-cell patch-clamp recording from neurons of aging rats, relative to young rats, the application of 3 microM GABA, causes twofold increases in the whole-cell membrane Cl- conductances and a loss of the physiologically important neuronal ability to desensitize to repeated GABA applications. These age-related alterations in neuronal membrane functions are amplified by 150% in the presence of agonists of BDZ recognition sites located on GABA receptor. The GABA deafferentation hypothesis also accounts for the age- and AD-related degeneration in the forebrain ascending cholinergic, glutamatergic, and the ascending mesencephalic monoaminergic system, despite that the latter, to foster the distribution-utilization of locally produced trophins, evolved syncytium-like connectivities among neuronal somata, axon collaterals, and dendrites, to bidirectionally transport trophins. (ABSTRACT TRUNCATED)
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PMID:GABAergic deafferentation hypothesis of brain aging and Alzheimer's disease revisited. 952 11

Vesicular monoamine transporters (VMATs) are involved in chemical transduction in monoaminergic neurons and various endocrine cells through the storage of monoamines in secretory vesicles. Mammalian pinealocytes contain more 5-hydroxytryptamine (5-HT) than any other cells and are expected to contain VMAT, although no information is available so far. Upon the addition of ATP, radiolabeled 5-HT was taken up by a particulate fraction prepared from cultured rat pinealocytes. The 5-HT uptake was inhibited significantly by bafilomycin A1 (an inhibitor of vacuolar H+-ATPase), 3,5-di-tert-butyl-4-hydroxybenzylidenemalononitrile (a proton conductor), or reserpine (an inhibitor of VMAT). RT-PCR analysis suggested that VMAT type 1 (VMAT1), but not type 2, is expressed. Antibodies against VMAT1 recognized a single polypeptide with an apparent molecular mass of approximately 55 kDa, and specifically immunostained pinealocytes. VMAT1 immunoreactivity was high in the vesicular structures in the varicosities of long branching processes and was associated with 5-HT, but not with synaptophysin, a marker protein for microvesicles. The 5-HT immunoreactivity in the long branching processes disappeared upon incubation with reserpine. These results indicate that 5-HT, at least in part, is stored in vesicles other than microvesicles in pinealocytes through a mechanism similar to that of various secretory vesicles.
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PMID:Vesicular monoamine transporter 1 is responsible for storage of 5-hydroxytryptamine in rat pinealocytes. 1058 16

The physiological action of extracellular ATP and other nucleotides in the nervous system is controlled by surface-located enzymes (ecto-nucleotidases) of which several families with partially overlapping substrate specificities exist. In order to identify ecto-nucleotidases potentially associated with neural cells, we chose PC12 cells for analysis. PC12 cells revealed surface-located ATPase and ADPase activity with apparent K(m)-values of 283 microM and 243 microM, respectively. Using PCR we identified the mRNA of all members of the ecto-nucleoside triphosphate diphosphohydrolase family investigated (NTPDase1 to NTPDase3, NTPDase5/6), of ecto-nucleotide pyrophosphatase/phosphodiesterase3 (NPP3), tissue-non-specific alkaline phosphatase and ecto-5'-nucleotidase. The surface-located catalytic activity differed greatly between the various enzyme species. Our data suggest that hydrolysis of ATP and ADP is mainly due to members of the ecto-nucleoside triphosphate diphosphohydrolase family. Activity of ecto-5'-nucleotidase and alkaline phosphatase was very low and activity of NPP3 was absent. For a detailed analysis of the cellular distribution of ecto-nucleotidases single and double transfections of PC12 cells were performed, followed by fluorescence analysis. Ecto-nucleotidases were distributed over the entire cell surface and accumulated intracellularly in varicosities and neurite tips. PC12 cell ecto-nucleotidases are likely to play an important role in terminating autocrine functions of released nucleotides and in producing extracellular nucleosides supporting the survival and neuritic differentiation of PC12 cells.
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PMID:Multiple ecto-nucleotidases in PC12 cells: identification and cellular distribution after heterologous expression. 1155 76

Early onset generalized dystonia is a severe form of primary dystonia linked to a mutation of the DYT1(TOR1A) gene on chromosome 9q34. DYT1 gene codifies for human torsinA, an AAA+ ATPase associated with the membranes of endoplasmic reticulum (ER) and the synaptic vesicles and proposed to be involved in trafficking of tubular-vesicular membrane through neuronal processes. In this study, the presence and the intracellular distribution of torsinA protein in SH-SY5Y neuroblastoma cells were evaluated by immunofluorescence and Western blot analysis following differentiation with retinoic acid and BDNF. Protein expression was then inhibited by transient antisense transfection and the possible effect on neurite outgrowth was observed. In SH-SY5Y cells torsinA, with an apparent MW of 38 kDa, is endogenously present and distributed, with a punctate pattern, in the cytosol and along the neurites. The protein showed high intensity of immunoreactivity in the neurite varicosities and was partially co-localized with vesicles markers. Terminally differentiated cells showed an increase of protein expression. Oligonucleotide antisense treatment induced a significant response to differentiating stimuli, lead to sprouting of longer neurites and increase in growth cone areas. A relationship between torsinA and tau protein, which is involved in axon elongation and establishment of neuronal polarity, was demonstrated by co-immunoprecipitation experiments. These findings suggest that torsinA, throughout the interaction with microtubule associated proteins, may contribute to control neurite outgrowth and could be involved in maintaining cell polarity.
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PMID:TorsinA negatively controls neurite outgrowth of SH-SY5Y human neuronal cell line. 1515 63


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