Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The glycoprotein nature of the binding subunit of the dopamine D2 receptor in rat striatum has been examined by photoaffinity labeling receptor preparations with N-(p-azido-m-[125I]iodophenethyl)spiperone followed by treatment of crude membrane receptor or receptor fractions isolated from sodium dodecyl sulfate (SDS) polyacrylamide gels with endo- and exoglycosidases. The major photoaffinity labeled protein migrates as a heterogeneous species on 10% SDS polyacrylamide gels and ranges from 130,000 to 75,000 relative molecular mass (Mr). This heterogeneity can be explained by glycosylation of the receptor by complex-type N-linked oligosaccharides. Three fractions of labeled receptor were isolated from SDS polyacrylamide gels over a range of 130,000 to 75,000 Mr; after digestion with peptide-N4-[N-acetyl-beta-glucosaminyl] asparagine amidase, all fractions yielded a single peptide approximately 40,000 Mr. Treatment of photoaffinity labeled membranes with alpha-mannosidase was without effect. The dopamine D2 receptor appears to contain substantial amounts of sialic acid as treatment of photoaffinity labeled membranes with neuraminidase increased the receptor mobility on SDS polyacrylamide gels to a species of 50,000-54,000 Mr. Treatment of the receptor with neuraminidase followed by endo-alpha-N-acetylgalactosaminidase did not change the electrophoretic migration pattern from that seen after neuraminidase treatment alone, suggesting that the binding peptide contains no serine- or threonine-linked oligosaccharides. A smaller binding peptide of approximately 31,000 Mr is also apparent in crude photoaffinity labeled membranes. This material also contains N-linked oligosaccharide. Complete removal of N-linked oligosaccharide from the dopamine D2 receptor did not change the rank order potency of agonist and antagonist compounds to compete for [3H]spiperone binding to crude membrane fractions. The dopamine D2 receptor represents a highly glycosylated neural receptor.
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PMID:N-linked oligosaccharides are responsible for rat striatal dopamine D2 receptor heterogeneity. 252 26

The ligand-binding subunit of the porcine striatal dopamine D2 receptor was identified by photoaffinity labeling with [125I]N-azidophenethylspiperone ([125I]NAPS). Upon photolysis, [125I]NAPS covalently incorporated into a broad band of apparent Mr congruent 140,000 with an appropriate pharmacological profile for D2 receptors as assessed by autoradiography after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Smaller subunits of apparent Mr congruent 94,000 and 34,000 were specifically labeled by [125I]NAPS with an appropriate D2 receptor profile and were similar to the major ligand-binding subunits of photoaffinity-labeled canine striatal D2 receptors. Photoaffinity labeling in the absence or presence of multiple protease inhibitors did not alter the migration pattern of the Mr congruent to 140,000/94,000 subunits upon denaturing electrophoresis in either the absence or presence of thiol-reducing/alkylating reagents. In order to investigate the possible basis for the existence of these high molecular weight forms of the D2 receptor, we assessed the carbohydrate nature of photolabeled D2 ligand-binding subunits by the use of lectin affinity chromatography and specific exo- and endoglycosidase treatments. Both photoaffinity-labeled D2 receptor proteins from porcine striatum (Mr congruent to 140,000 and 94,000) were glycoproteins as indexed by their absorption and specific elution from wheat germ agglutinin lectin resins. The exoglycosidase neuraminidase altered the electrophoretic mobility of both the Mr congruent to 140,000 and 94,000 labeled subunits to a single band of apparent Mr congruent to 51,000. Prior removal of sialic acid residues did not alter the reversible binding characteristics of [3H]spiperone to D2 receptors. Complete removal of receptor-associated N-linked carbohydrate by the endoglycosidase glycopeptidase F (peptide-N4[N-acetyl-beta-glucosaminyl]asparagine amidase) produced a further increase in the mobility of the Mr congruent to 51,000 subunit to apparent Mr congruent to 44,000. The porcine Mr congruent to 34,000 photolabeled peptide is an N-linked glycoprotein as assessed by lectin affinity chromatography and susceptibility to digestion by glycopeptidase F to a peptide of apparent Mr congruent to 23,000.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dopamine D2 receptor binding subunits of Mr congruent to 140,000 and 94,000 in brain: deglycosylation yields a common unit of Mr congruent to 44,000. 297 May 86

The long arm of chromosome 11 is one of the most interesting regions in the search for major genes involved in the etiology of manic-depressive illness. Several candidate genes have been identified, including the gene encoding the dopamine D2 receptor, the M1 muscarinic receptor, and porfobillinogen deaminase. Furthermore, different families with co-segregation of psychiatric illness and structural chromosome abnormalities involving regions 11q21, 11q22.3, and 11q25 have been reported. Using narrow as well as broad phenotypic models, conservative genetic parameters, models with dominant or recessive modes of inheritance, and various methods to reduce misclassification, the present study did not find evidence for a major gene causing manic-depressive illness on the long arm of chromosome 11. In the broader phenotypic models multi-point analyses excluded at least 11q14 to 11q23.3, approximately 60 cM, even in one large family. Assuming homogeneity close linkage to DRD2 was excluded for all dominant models, and also in the affecteds-only analyses in the large family alone.
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PMID:Linkage analysis between manic-depressive illness and markers on the long arm of chromosome 11. 854 51

The present study was undertaken to examine the role of the benzodiazepine/GABA and N-methyl-d-aspartate (NMDA) systems in the convulsive effect of cocaine in mice. When cocaine (3.5 mg/ml) solution was infused into the tail vein at a rate of 0.3 ml/min, mice showed clonic and tonic convulsions. These seizures were not affected by low doses of bicuculline or picrotoxin, a GABAA receptor antagonist and a Cl ion channel blocker, respectively. Aminooxyacetic acid (AOAA), a GABA deaminase inhibitor, and phenobarbital, a Cl ion channel activator, and baclofen, a GABAB receptor agonist, also had no effect on these convulsions. Benzodiazepine inverse agonist beta-DMCM, at a dose which by itself had no convulsive effect lowered the convulsive threshold of cocaine. This lowered convulsive threshold was reversed by flumazenil, a benzodiazepine inverse antagonist, and diazepam, a benzodiazepine full agonist, which by themselves did not inhibit cocaine seizure. It is likely that cocaine seizure involves a benzodiazepine (beta-carboline) recognition site other than the benzodiazepine/GABAA receptor-Cl ionophore complex system. CPP and MK-801, competitive and noncompetitive NMDA receptor antagonists, respectively, inhibited cocaine seizures. The inhibitory effects of CPP on cocaine convulsion were reversed by a low dose of NMDA, which by itself did not induce seizure. A dopamine D1 receptor agonist SKF38393 enhanced both clonic and tonic convulsions, while a dopamine D2 receptor agonist bromocriptine inhibited these convulsions. These stimulatory and inhibitory effects were reversed by the D1 and D2 receptor antagonists, SCH23390 and haloperidol, respectively. These results suggest that the cocaine-induced convulsion may involve an activation of the NMDA-Ca ionophore complex system, which is mediated by the dopaminergic system, and a beta-carboline recognition site other than the benzodiazepine/GABAA receptor-Cl ionophore complex system.
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PMID:Cocaine: evidence for NMDA-, beta-carboline- and dopaminergic-mediated seizures in mice. 966 68