Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male rats administered with a single i.p. dose of 5 mg/kg methyl parathion, showed the toxic signs of hypercholinergic (anticholinesterase) activity with maximal severity, including muscle fasciculations and convulsions within 15 to 30 min, persisting for about 2 hr. The time course of acetylcholinesterase activity in discrete brain regions (cortex, stem, striatum and hippocampus), heart and hemidiaphragm, indicated its maximal depression during 30 to 60 min after administration of methyl parathion. At this time, a marked reduction in carboxylesterase activity was also evident both in neuronal and nonneuronal tissues, suggesting a tremendous binding to nonacetylcholinesterase serine sites. Pretreatment with memantine hydrochloride (18 mg/kg, i.p.) 30 min, and atropine sulfate (16 mg/kg, i.p.) 15 min before methyl parathion administration, completely prevented the expected toxic signs and significantly (P less than 0.01) attenuated the induced inhibition of acetylcholinesterase. When given therapeutically, this combined treatment completely reversed the clinical evidence of methyl parathion toxicity within 10 to 15 min and markedly reduced the acetylcholinesterase inactivation. These results suggest that memantine may counteract the acute methyl parathion toxicity by (a) protection of acetylcholinesterase from inhibition, (b) rapid reactivation of inhibited acetylcholinesterase and (c) rapid bioelimination of methyl parathion, in addition to cholinolytic effects of atropine sulfate.
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PMID:Methyl parathion acute toxicity: prophylaxis and therapy with memantine and atropine. 224 28

The biochemical and morphological effects of postnatal acetylcholinesterase (AChE) inhibition were examined in rat pups dosed with paration, at time points critical to hippocampal neurogenesis and synaptogenesis (i.e., day 5-20). In treated pups, sacrificed on day 21, hippocampal histopathology, as assessed by light and electron microscopy, consisted of cellular disruption and necrosis in the dentate gyrus (DG), and CA4 regions. Synaptic disruption in the DG molecular layer was suggested by histochemical preparation using both the Timm's and AChE stains. In parathion-treated pups, sampled at day 12, hippocampal AChE was depressed 73% and [3H] quinuclidiny benzilate (QNB) binding was depressed by 36%. The above results indicate that morphological and biochemical consequences are associated with persistent AChE depression in neonatal rats.
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PMID:The neurotoxicity of parathion-induced acetylcholinesterase inhibition in neonatal rats. 228 52

Rats injected intravenously with monoclonal antibodies reactive with brain acetylcholinesterase (AChE) developed a prolonged depression of plasma AChE without changes in butyrylcholinesterase, lactic acid dehydrogenase, or hematocrit. One antibody, ZR1, accumulated in the brain and spinal cord. Within 3 days of injection, ZR1 bound to most of the AChE in cerebral cortex and certain other regions of the CNS. Examination of the molecular forms of cortical 10S AChE, whereas 4S AChE remained free. In vitro, however, ZR1 bound equally to solubilized 4S and 10S forms. These data provide direct evidence for the compartmentalization of different AChE forms in the CNS, 10S being mainly extracellular and 4S apparently intracellular. Development of a striking and persistent bilateral ptosis within hours of injection suggests that AChE in the autonomic nervous system is also accessible to antibodies and, furthermore, is the site of an immunopathological lesion. This novel model of cholinergic autoimmunity may have relevance for human neurological disorders of unknown etiology.
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PMID:Selective complexing of acetylcholinesterase in brain by intravenously administered monoclonal antibody. 229 14

Four test groups of small songbirds (Zebra Finch, Poephila guttata) were sprayed in a chamber with varying concentrations of fenitrothion. Exposure levels were assessed by monitoring air concentrations, deposits of the active ingredient (AI) on glass plates and droplets/cm2 on Kromekote cards. All indices of exposure were linearly correlated and the mean AI deposit on glass plates for the four groups tested with equivalent to 38, 51, 139 and 255 g/ha or 14%, 18%, 50% and 91% of the highest permissible emitted rate for broadscale forest spraying in Canada. Significant depression in body weights and brain acetylcholinesterase levels were noted only for the highest exposure group. Fenitrothion residues in blood were detectable only at the highest exposure level, and in liver at the two higher levels. Carcass and feather residues were much higher than those in blood and liver, and were detectable at all exposure levels but the residues did not increase linearly with exposure. For one of the spray groups, we were able to compute an equivalent acute oral dose based on matching acetylcholinesterase inhibition.
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PMID:An improved method to study the impact of pesticide sprays on small song birds. 234 1

Depression of platelet function with a single intraperitoneal injection of acetylsalicylic acid was found to produce significant increases in several thrombocytopoietic indicators despite no observed change in platelet counts. There was an increase in the number of megakaryocytic precursor cells (small acetylcholinesterase positive or "SAChE+" cells), platelet size, and 35S incorporation into platelets. The results are qualitatively comparable to data from previous experiments showing that treatment of mice with a thrombocytopoiesis-stimulating factor (TSF or thrombopoietin) and rabbit anti-mouse platelet serum will elevate thrombocytopoiesis. The results presented herein indicate that interruption of platelet function by aspirin results in the production of new platelets, presumably by the action of a feedback system controlling thrombocytopoiesis.
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PMID:Acetylsalicylic acid stimulates murine megakaryocyte precursor cells. 235 90

The neurotoxic effects of long-term, low-level exposure to the commercially available insecticide, Fenthion, were examined in the present study. Young (2 month) adult, male Long-Evans rats were dermally exposed to Fenthion (25 mg/kg, 3X week) and sampled after 2 and 10 months exposure to assess neurotoxic damage in the hippocampus using morphological and biochemical endpoints. Histopathology, consisting of gliosis, swollen and necrotic neurons, and cell dropout, occurred in the dentate gyrus (DG), CA4 (hilus), and CA3 sectors as early as 2 months postexposure. Acetylcholinesterase (AChE) staining of brain tissues taken at this time was severely reduced in the septal nuclei, the DG molecular layer, the CA4, and the hippocampus proper. After 10 months exposure to Fenthion, cellular necrosis and gliosis intensified in the CA4 and CA3 regions and occasionally involved the CA2. Radiometric assays of AChE activity in the hippocampus indicated a 65 and 85% depression after 2 and 10 months exposure, respectively. Quinuclidinyl benzilate binding for the hippocampal muscarinic receptor was reduced by 6 and 15%, after 2 and 10 months exposure, respectively. A separate group of older (12 month) rats was exposed to the same dosing regimen of Fenthion and examined for neuropathological damage after 2 and 10 months exposure. Aged animals exposed for only 2 months expressed severe hippocampal degeneration in a pattern similar to that seen in the young adult after 10 months exposure (viz., DG, CA4, CA3). Aged animals exposed for 10 months showed more extensive histopathology of the CA4-2 and occasionally CA1. These observations indicate that in both young adult and aged animals, subchronic, low-level exposure to anticholinesterase compounds can result in serious neurotoxic consequences to the mammalian hippocampus.
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PMID:The neurotoxicity of subchronic acetylcholinesterase (AChE) inhibition in rat hippocampus. 238 36

The mechanisms responsible for slowing cardiac impulse conduction through the atrioventricular (AV) node are not well understood but include anatomical architecture, presence of cells with diverse electrophysiological characteristics, and modulation by autonomic nervous system. The present study was designed to determine the site of vagally induced slowing of conduction through the AV node. We attempted to correlate the electrophysiological response of AV nodal cells to postganglionic vagal stimulation applied in different regions of the node with the morphological findings and patterns of acetylcholinesterase-positive staining of nodal tissue. This multifaceted approach revealed that vagal stimulation produced localized hyperpolarization of the cells from the N region of the AV node, which correlated with the strong acetylcholinesterase positive staining of the central nodal area. In contrast, the density of the acetylcholinesterase staining decreased toward both the AN and His bundle regions, whereas vagal stimulation had a negligible effect on the cells from these regions. These results suggest that vagal-induced depression of AV nodal conduction is produced by release of acetylcholine predominantly around the midnodal region and the depressive action of acetylcholine is concentrated on the cells occupying the same region (i.e., the N cells). Thus, there appears to be a close juxtaposition of nerve elements and effector cells in the midnodal region of the AV node. This unique combination of available neuromediator and responding cells with hyperpolarization and depressed action potential determines the midnodal region as the focus of vagal effect on AV nodal conduction.
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PMID:Morphological and electrophysiological correlates of atrioventricular nodal response to increased vagal activity. 239 13

When an automated counting instrument using an esterase stain was employed, decreased monocyte counts were observed in a group of process workers exposed to organophosphate esters. Their monocyte counts were not found to be depressed with manual counting or with an automated counter using another staining method. The apparent depression was transient. In these workers and a comparison group, theoretical adverse consequences of decreased monocyte esterase and also possible changes in other esterases were explored. No anergy was seen with mumps or staphylococcal phage lysate hypersensitivity skin tests. Histology of the mumps reaction was similar in both groups. The depressed monocyte counts were significantly associated with a mild reduction in erythrocyte cell acetylcholinesterase, but no reduction was seen in plasma pseudocholinesterase or lymphocyte neurotoxic esterase.
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PMID:Industrial exposure to organophosphorus compounds. Studies of a group of workers with a decrease in esterase-staining monocytes. 241 79

Interactions of the oximes pyridine-2-aldoxime (2-PAM) and 1-(2-hydroxyiminomethyl-1-pyridino)-3-(4-carbamoyl-1-pyridino++ +)-2-oxapropane dichloride (HI-6), reactivators of phosphorylated acetylcholinesterase enzyme, with the nicotinic acetylcholine receptor-ion channel complex were studied using electrophysiological techniques. Single channel studies revealed that both oximes increased the opening probability of channels that were activated by acetylcholine. The oximes reduced mean channel open time and burst time in a concentration- and voltage-dependent manner. End-plate current amplitude was increased by 2-PAM (10-100 microM) and HI-6 (1 microM) but depressed at higher concentrations of these agents. The oximes decreased the time constant of end-plate current decay, particularly at hyperpolarized membrane potentials. HI-6 depressed indirect twitch response of the sartorius muscle, whereas 2-PAM caused a facilitation followed by depression. Both agents directly hydrolyzed acetylthiocholine, in addition to weakly inhibiting acetylcholinesterase. Our study demonstrates a direct molecular interaction of the oximes HI-6 and 2-PAM with the natural agonist molecule and with the acetylcholine receptor-ion channel complex. These effects can explain the excitatory and inhibitory actions of both agents, and may form the basis for their antidotal effectiveness against organophosphorus poisoning. The quantitative differences between the effects of 2-PAM and HI-6 on the above parameters are important in view of their differential antidotal efficacies.
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PMID:Acetylcholinesterase reactivators modify the functional properties of the nicotinic acetylcholine receptor ion channel. 245 74

The effects of lethal (2.0 mg/kg) and high sublethal (1.3 mg/kg) dosages of the organophosphate acetylcholinesterase (AChE) inhibitor paraoxon on FR10 performance rate was determined 1 and 2 days after intoxication. The lethal doses were antidoted with either centrally acting atropine sulfate (AS), or atropine methyl bromide (AMB) or atropine methyl nitrate (AMN), both quaternary salts and not expected to act centrally. AChE inhibition in the brain was about 35-60% on the second day after treatment. AS yielded a small transient depression in performance, while AMB and AMN yielded severe deficits, with incomplete recovery. Performance was depressed by 1.3 mg/kg paraoxon by 52% and 34% on days 1 and 2, respectively, while performance was more greatly depressed by the lethal dose, especially with the noncentrally acting antidotes: AS, 67 and 48%; AMB, 81 and 55%; AMN, 91 and 78%. However, a low dose of AS with 2 mg/kg paraoxon resulted in very severe, nonrecovering deficits. A lethal dose of the nonpersistent anti-AChE eserine sulfate, antidoted with a low dose of AS, yielded no deficits. Thus, a high level, acute intoxication with paraoxon yields behavioral deficits which are attenuated by high levels of a centrally acting muscarinic receptor antagonist. The paraoxon-induced performance deficits or their recovery do not correlate directly with AChE inhibition.
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PMID:Short-term effects of paraoxon and atropine on schedule-controlled behavior in rats. 259 81


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