Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The combination of both Cl- and HCO3- secretion inhibitors causes an accumulation of mucins within the submucosal gland ducts of acetylcholine (ACh)-treated bronchi [S. K. Inglis, M. R. Corboz, A. E. Taylor, and S. T. Ballard. Am. J. Physiol. 272 (Lung Cell. Mol. Physiol. 16): L372-L377, 1997], suggesting indirectly that these agents block airway gland liquid secretion. The present study tested the hypotheses that ACh-stimulated liquid secretion is driven by Cl- and HCO3- secretion and that inhibition of this process leads to secretion of a dehydrated mucus with altered rheological properties. Excised distal bronchi from pigs were pretreated with either a combination of Cl- and HCO3- secretion inhibitors (bumetanide, acetazolamide, dimethylamiloride, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid) or the dimethyl sulfoxide vehicle and were then treated with ACh to induce secretion. The rate of mucus liquid secretion was substantially reduced when the airways were pretreated with the anion secretion inhibitors. Mucus liquid from inhibitor-pretreated airways contained almost threefold more nonvolatile solids than the control liquid. Rheological analysis revealed that mucus liquid from inhibitor-pretreated airways expressed a significantly greater log G* (rigidity factor), whereas tangent delta (recoil factor) was significantly reduced. These results suggest that 1) ACh-induced liquid secretion in bronchi is driven by both Cl- and HCO3- secretion and 2) inhibition of ACh-induced liquid secretion results in the secretion of mucus with a reduced water content and altered rheological properties.
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PMID:Inhibition of airway liquid secretion and its effect on the physical properties of airway mucus. 948 11

It has not been well established whether the mechanisms participating in pH regulation in the anoxic-reoxygenated developing myocardium resemble those operating in the adult. We have specially examined the importance of Na+/H+ exchange (NHE) and HCO3-dependent transports in cardiac activity after changes in extracellular pH (pHo). Spontaneously contracting hearts isolated from 4-day-old chick embryos were submitted to single or repeated anoxia (1 min) followed by reoxygenation (10 min). The chronotropic, dromotropic and inotropic responses of the hearts were determined in standard HCO3- buffer at pHo 7.4 and at pHo 6.5 (hypercapnic acidosis). In distinct experiments, acidotic anoxia preceded reoxygenation at pHo 7.4. NHE was blocked with amiloride derivative HMA (1 micro mol/l) and HCO3-dependent transports were inactivated by replacement of HCO3 or blockade with stilbene derivative DIDS (100 micro mol/l). Anoxia caused transient tachycardia, depressed mechanical function and induced contracture. Reoxygenation temporarily provoked cardiac arrest, atrio-ventricular (AV) block, arrhythmias and depression of contractility. Addition of DIDS or substitution of HCO3 at pHo 7.4 had the same effects as acidosis per se, i.e. shortened contractile activity and increased incidence of arrhythmias during anoxia, prolonged cardioplegia and provoked arrhythmias at reoxygenation. Under anoxia at pHo 6.5/reoxygenation at pHo 7.4, cardioplegia, AV block and arrhythmias were all markedly prolonged. Interestingly, in the latter protocol, DIDS suppressed AV block and arrhythmias during reoxygenation, whereas HMA had no effect. Thus, intracellular pH regulation in the anoxic-reoxygenated embryonic heart appears to depend predominantly on HCO3 availability and transport. Furthermore, pharmacological inhibition of anion transport can protect against reoxygenation-induced dysfunction.
J Mol Cell Cardiol 1998 Feb
PMID:Inhibition of bicarbonate transport protects embryonic heart against reoxygenation-induced dysfunction. 951 9

The Calu-3 cell line is being investigated as a model for human submucosal gland serous cells. In a previous investigation of basal short-circuit current (Isc) in Calu-3 cells, high levels of bumetanide-insensitive basal Isc (approximately 60 microA/cm2) were measured in cells grown at an air interface. Basal Isc was reduced only 7% by bumetanide, and the largest component of basal Isc required both Cl- and HCO3- in the bathing solutions. Because Isc could be partially inhibited by basolateral 4,4'-dinitrostilbene-2,2'-disulfonic acid and because the only known apical exit pathway for anions is the cystic fibrosis transmembrane conductance regulator, which has a relatively poor conductance for HCO3-, it was concluded that most basal Isc is HCO3(-)-dependent Cl- secretion [M. Singh, M. Krouse, S. Moon, and J. J. Wine. Am. J. Physiol. 272 (Lung Cell. Mol. Physiol. 16): L690-L698, 1997]. We have now measured isotopic fluxes of 36Cl- and 22Na+ across short-circuited Calu-3 cells and found that virtually none of the basal Isc is Cl- secretion or Na+ absorption. Thus, in contrast to the earlier report, we conclude that the major component of basal Isc is HCO3- secretion. Stimulation recruits primarily Cl- secretion, as previously proposed.
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PMID:Evidence that Calu-3 human airway cells secrete bicarbonate. 953 Jan 82

Infrared microspectroscopy combines microscopy and spectroscopy for the purpose of chemical microanalysis. Light microscopy provides a way to generate and record magnified images and visibly resolve microstructural detail. Infrared spectroscopy provides a means for analyzing the chemical makeup of materials. Combining light microscopy and infrared spectroscopy permits the correlation of microstructure with chemical composition. Inherently, the long wavelengths of infrared radiation limit the spatial resolution of the technique. However, synchrotron infrared radiation significantly improves both the spectral and spatial resolution of an infrared microspectrometer, such that data can be obtained with high signal-to-noise at the diffraction limit, which is 3-5 microm in the mid-infrared region. In this study, we use infrared microspectroscopy to study the chemical composition of bone using two mapping methods. In the osteon method, linear maps are collected from the center of an osteon (newer bone) to the periphery (older bone) and their chemical compositions are compared. In the transverse method, applied specifically to subchondral bone, line maps are collected from the edge of the articular cartilage (older bone) to the marrow space (newer bone). A significant advantage of infrared microspectroscopy over other chemical methods is that the bone does not need to be homogenized for testing; we are able to study cross-sectional samples of bone in situ at a resolution better than 5 microm and compare the results with morphological findings on stained serial sections immediately adjacent to those examined by infrared microspectroscopy. The infrared absorption bands of bone proteins and mineral are sensitive to mineral content (i.e. carbonate, phosphate, acid phosphate), mineral crystallinity and the content/nature of the organic matrix. In this study, they are analyzed as a function of (1) age, i.e. distance with respect to the center of an osteon, and (2) morphology, i.e. cortical versus cancellous (notably subchondral) bone. Results show that the protein/mineral ratio is higher in younger bone. As bone matures, mineralization increases, as does carbonate substitution into the hydroxyapatite lattice. Finally, most of the changes in chemical composition of bone occur within 20 microm of the site of new bone growth, e.g. the center of an osteon, demonstrating the need for the high spatial resolution achieved only with the use of a synchrotron infrared source.
Cell Mol Biol (Noisy-le-grand) 1998 Feb
PMID:A method for examining the chemical basis for bone disease: synchrotron infrared microspectroscopy. 955 44

In porcine bronchi, inhibition of both Cl- and HCO3- transport is required to block the anion secretion response to ACh and to cause mucus accumulation within ACh-treated submucosal gland ducts [S. K. Inglis, M. R. Corboz, A. E. Taylor, and S. T. Ballard. Am. J. Physiol. 272 (Lung Cell. Mol. Physiol. 16): L372-L377, 1997]. In this previous study, a combination of three potential HCO3- transport inhibitors [1 mM acetazolamide, 1 mM DIDS, and 0.1 mM dimethylamiloride (DMA)] was used to block carbonic anhydrase, Cl-/HCO3- exchange, and Na+/H+ exchange, respectively. The aim of the present study was to obtain a better understanding of the mechanism of ACh-induced HCO3- secretion in airway glands by determining which of the three inhibitors, in combination with bumetanide, is required to block anion secretion and so cause ductal mucin accumulation. Gland duct mucin content was measured in distal bronchi isolated from domestic pigs. Addition of either bumetanide alone, bumetanide plus acetazolamide, or bumetanide plus DIDS had no significant effect on ACh-induced mean gland duct mucin content. In contrast, glands treated with bumetanide plus DMA as well as glands treated with all four anion transport blockers were almost completely occluded with mucin after the addition of ACh. These data suggest that mucin is cleared from the ducts of bronchial submucosal glands by liquid generated from Cl(-)- and DMA-sensitive HCO3- transport.
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PMID:Effect of anion secretion inhibitors on mucin content of airway submucosal gland ducts. 961 91

A 3.3 kb HindIII restriction-digest DNA fragment was isolated from a Synechocystis sp. strain PCC6803 subgenomic plasmid library which strongly hybridized to a 349 bp fragment of the icfA (ccaA) gene from Synechococcus sp. strain PCC7942. DNA sequence analysis of the fragment revealed three open reading frames (ORFs), two of which potentially coded for pantothenate synthetase (ORF275) and cytidylate kinase (ORF230). The third, ORF274, was 825 bp in length, encoding a deduced polypeptide of 274 aa (Mr, 30747) that bears 55% sequence identity to the Synechococcus icfA (ccaA) translation product, a beta-type carbonic anhydrase (CA). A 932 bp EcoRI fragment containing ORF274 was subcloned into an expression vector and the construct was transformed into Escherichia coli for overexpression. Electrometric assays for CA activity revealed that whole cell extracts containing the recombinant protein significantly enhanced the rate of conversion of CO2 to HCO3- and that 98% of this catalytic activity was inhibited by ethoxyzolamide, a well-characterized CA inhibitor. Antisera derived against the overexpressed protein recognized a 30.7 kDa protein that was predominantly associated with the isolated carboxysome fraction from Synechocystis. These results provide molecular and physiological evidence for the identification of a ccaA homologue in Synechocystis PCC6803 that encodes a carboxysomal beta-type CA.
Plant Mol Biol 1998 May
PMID:Cloning, characterization and expression of carbonic anhydrase from the cyanobacterium Synechocystis PCC6803. 961 94

We have recently reported the synthesis of urea from ammonia, glutamine and arginine in enterocytes of postweaning pigs. The present study was conducted to determine the compartmentation and kinetics of urea cycle enzymes in these cells. Carbamoyl phosphate synthase I (CPS I) and ornithine carbamoyltransferase (OCT) were located exclusively in mitochondria, whereas argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL) were found in the cytosol. Arginase isozymes were present in both the cytosol and mitochondria of enterocytes, and differed in their sensitivity to heat inactivation. Except for OCT, Vmax values of urea cycle enzymes were much lower in enterocytes than in the liver of pigs, and vice versa for their Km values. Because of a low rate of ureagenesis in enterocytes compared with the liver, intestinal urea cycle enzymes may function primarily to synthesize citrulline. The co-localization of CPS I and OCT and a high activity of OCT in enterocyte mitochondria favors the intestinal synthesis of citrulline from ammonia, HCO3- and ornithine. Low activities of cytosolic ASS and ASL minimize the conversion of citrulline into arginine and therefore, the recycling of citrulline into ornithine via arginase in postweaning-pig enterocytes. These kinetic properties of intestinal urea cycle enzymes maximize the net synthesis of citrulline from glutamine and explain the release of large amounts of citrulline by the pig small intestine. The two compartmentally separated arginase isozymes in enterocytes may play an important role in regulating the intestinal metabolism of proline, nitric oxide and polyamines.
Comp Biochem Physiol B Biochem Mol Biol 1998 Mar
PMID:Compartmentation and kinetics of urea cycle enzymes in porcine enterocytes. 973 36

We studied calcium signaling in a newly described pancreatic cell line, GK-P3, that expresses functional amino acid neurotransmitter receptors. GK-P3 cells express the first strychnine-sensitive glycine receptors reported in a permanent cell line. In addition, GK-P3 cells express alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors. Both types of amino acid receptors showed electrophysiological and pharmacological behavior similar to their neuronal counterparts. The glycine receptors were permeable to Cl- and blocked by the selective antagonist strychnine. AMPA receptors showed limited permeability to Ca2+, were blocked by 6-cyano-2, 3-dihydroxy-7-nitroquinoxaline, and were potentiated by cyclothiazide. Interestingly, activation of either receptor type increased intracellular Ca2+ measured by digital imaging of Fura-2 fluorescence. These Ca2+ signals were completely blocked by 30 microM La3+, suggesting that the Ca2+ entered the cells largely through voltage-dependent Ca2+ channels. Alterations in the extracellular concentrations of Cl- and/or HCO3- had only marginal effects on glycine-evoked Ca2+ signals. However, increases in intracellular Ca2+ mediated by AMPA receptors were absent when the extracellular Na+ was replaced with an impermeant cation, N-methyl-D-glucamine. We conclude that activation of ligand-gated cation or anion channels depolarize GK-P3 cells sufficiently to activate their voltage-gated Ca2+ channels leading to increases in intracellular Ca2+ concentration. Thus, glycine and glutamate receptors may regulate Ca2+-dependent secretory mechanisms in islet cells by altering the membrane potential of these cells. Our data in GK-P3 cells support the growing weight of evidence for a role of amino acid neurotransmitters in pancreatic islets and introduce strychnine-sensitive glycine receptors as a novel target of amino acid neurotransmitter regulation in islets.
Mol Pharmacol 1998 Oct
PMID:Activation of glycine and glutamate receptors increases intracellular calcium in cells derived from the endocrine pancreas. 976 6

Adrenergic stimulation of parotid secretion was investigated in anaesthetised brushtail possums to ascertain fluid secretion rates and salivary composition. Because neither alpha- nor beta-adrenergic stimulation evoked saliva output, infusion of the adrenergic agonists was superimposed on a pre-existing bethanechol-stimulated flow. Isoprenaline infusion (2.4 nmol min-1) increased salivary amylase activity, [protein]; [HCO3]; [PO4] and [Ca], and amylase/Ca and protein/Ca ratios; reduced [Cl]; [K] and osmolality; but did not alter H+ activity; [urea]; [Na]; [Mg]; amylase/protein or saliva/plasma urea ratios. These data are consistent with isoprenaline stimulating acinar secretion of protein, Ca and PO4 but not the ion transport necessary for primary fluid formation at the endpieces and modifying transport of monovalent ions in the excurrent ducts. Consequently, the possum parotid has beta-adrenergic receptors in both the endpieces and excurrent ducts. Phenylephrine infusions at 2.4 and 24 nmol min-1 were without effect whereas phenylephrine at 240 nmol min-1 caused changes in salivary composition which paralleled those for isoprenaline administration but were generally of lesser magnitude. Thus, the possum parotid has few or no alpha-adrenergic receptors and the salivary response elicited was the result of cross-reaction of phenylephrine with beta-adrenergic receptors.
Comp Biochem Physiol A Mol Integr Physiol 1998 Jun
PMID:Response of the parotid gland of the brushtail possum, Trichosurus vulpecula, to adrenergic stimulation. 977 9

Pex14p is a central component of the peroxisomal protein import machinery, which has been suggested to provide the point of convergence for PTS1- and PTS2-dependent protein import in yeast cells. Here we describe the identification of a human peroxisome-associated protein (HsPex14p) which shows significant similarity to the yeast Pex14p. HsPex14p is a carbonate-resistant peroxisomal membrane protein with its C terminus exposed to the cytosol. The N terminus of the protein is not accessible to exogenously added antibodies or protease and thus might protrude into the peroxisomal lumen. HsPex14p overexpression leads to the decoration of tubular structures and mislocalization of peroxisomal catalase to the cytosol. HsPex14p binds the cytosolic receptor for the peroxisomal targeting signal 1 (PTS1), a result consistent with a function as a membrane receptor in peroxisomal protein import. Homo-oligomerization of HsPex14p or interaction of the protein with the PTS2-receptor or HsPex13p was not observed. This distinguishes the human Pex14p from its counterpart in yeast cells and thus supports recent data suggesting that not all aspects of peroxisomal protein import are conserved between yeasts and humans. The role of HsPex14p in mammalian peroxisome biogenesis makes HsPEX14 a candidate PBD gene for being responsible for an unrecognized complementation group of human peroxisome biogenesis disorders.
Mol Cell Biol 1999 Mar
PMID:Identification and characterization of the human orthologue of yeast Pex14p. 1002 13


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