Correlation between organophosphate poisoning, acetylcholinesterase inhibition, and increased cyclic GMP levels in malathion-treated insects

1977 ◽  
Vol 55 (5) ◽  
pp. 534-542 ◽  
Author(s):  
Robert P. Bodnaryk
Keyword(s):  
Cyclic Gmp ◽  
Time Course ◽  
Acetylcholinesterase Activity ◽  
Acetylcholinesterase Inhibition ◽  
Organophosphate Poisoning ◽  
Abrupt Increase ◽  
Sarcophaga Bullata ◽  
Biochemical Lesion ◽  
Lag Period ◽  
Dose Dependent

Organophosphate poisoning with malathion caused large increases (up to 125 and 440%, respectively) in the level of cyclic GMP in larvae of Mamestra configurata Wlk. and in the fly Sarcophaga bullata Parker. Cyclic AMP was little affected. The malathion-induced increase in cyclic GMP was time and dose dependent. Time-course studies with the head and thorax of S. bullata demonstrated that the increase in cyclic GMP level occurred precipitously after a lag period of about 1 h, during which time the activity of acetylcholinesterase (EC 3.1.1.7) was progressively inhibited. The abrupt increase in cyclic GMP began when acetylcholinesterase activity had been inhibited to a sufficient extent to permit accumulation of acetylcholine. It is suggested that the accumulation of acetylcholine in the malathion-poisoned insects caused cyclic GMP levels to rise.Cyclic GMP may have a role in cholinergic transmission in normally functioning insect neural tissue. Increased levels of cyclic GMP induced by organophosphate and organochlorine (Bodnaryk, R. P. (1976) Can. J. Biochem. 54, 957–962) insecticides appear to be a vital and previously unrecognized biochemical lesion in insects poisoned by these compounds.

scholarly journals The Toxic Effect of Manganese on the Acetylcholinesterase Activity in Rat Brains

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Vahid Yousefi Babadi ◽  
Leila Sadeghi ◽  
Kobra Shirani ◽  
Ali Akbar Malekirad ◽  
Mohammad Rezaei
Keyword(s):  
Toxic Effect ◽  
Ache Activity ◽  
Time Course ◽  
Acetylcholinesterase Activity ◽  
Time Intervals ◽  
Chronic Dose ◽  
Essential Nutrient ◽  
Short Time ◽  
Chronic Doses ◽  
Dose Dependent

Manganese (Mn) is a naturally occurring element and an essential nutrient for humans and animals. However, exposure to high levels of Mn may cause neurotoxic effects. Accumulation of manganese damages central nervous system and causes Parkinson’s disease-like syndrome called manganism. Mn neurotoxicity has been suggested to involve an imbalance between the DAergic and cholinergic systems. The pathological mechanisms associated with Mn neurotoxicity are poorly understood, but several reports have established it is mediated by changing of AChE activity that resulted in oxidative stress. Therefore we focused the effect of Mn in AChE activity in the rat’s brain by MnCl2injection intraperitoneally and analyzed their brains after time intervals. This study used different acute doses in short time course and different chronic doses at different exposing time to investigate which of them (exposing dose or time) is more important in Mn toxic effect. Results showed toxic effect of Mn is highly dose dependent and AChE activity in presence of chronic dose in 8 weeks reaches acute dose in only 2 days.

scholarly journals Complexing of the CD-3 subunit by a monoclonal antibody activates a microtubule-associated protein 2 (MAP-2) serine kinase in Jurkat cells

1989 ◽  
Vol 262 (2) ◽  
pp. 449-456 ◽  
Author(s):  
C Hanekom ◽  
A Nel ◽  
C Gittinger ◽  
A Rheeder ◽  
G Landreth
Keyword(s):  
T Cells ◽  
Time Course ◽  
Gel Filtration ◽  
Maximal Activity ◽  
Jurkat Cells ◽  
Serine Kinase ◽  
Transient Activation ◽  
Normal Human ◽  
Dose Dependent

Treatment of Jurkat T-cells with anti-CD-3 monoclonal antibodies resulted in the rapid and transient activation of a serine kinase which utilized the microtubule-associated protein, MAP-2, as a substrate in vitro. The kinase was also activated on treatment of Jurkat cells with phytohaemagglutinin, but with a different time course. The activation of the MAP-2 kinase by anti-CD-3 antibodies was dose-dependent, with maximal activity observed at concentrations of greater than 500 ng/ml. Normal human E-rosette-positive T-cells also exhibited induction of MAP-2 kinase activity during anti-CD-3 treatment. The enzyme was optimally active in the presence of 2 mM-Mn2+; lower levels of activity were observed with Mg2+, even at concentrations up to 20 mM. The kinase was partially purified by passage over DE-52 Sephacel with the activity eluting as a single peak at 0.25 M-NaCl. The molecular mass was estimated to be 45 kDa by gel filtration. The activation of the MAP-2 kinase was probably due to phosphorylation of this enzyme as treatment with alkaline phosphatase diminished its activity. These data demonstrate that the stimulation of T-cells through the CD-3 complex results in the activation of a novel serine kinase which may be critically involved in signal transduction in these cells.

Retinoic acid application to chick wing buds leads to a dose-dependent reorganization of the apical ectodermal ridge that is mediated by the mesenchyme

Development ◽  
1989 ◽  
Vol 106 (4) ◽  
pp. 691-705 ◽  
Author(s):  
C. Tickle ◽  
A. Crawley ◽  
J. Farrar
Keyword(s):  
Retinoic Acid ◽  
Gap Junctions ◽  
Time Course ◽  
Apical Ectodermal Ridge ◽  
Threshold Response ◽  
Epithelial Morphology ◽  
Early Effects ◽  
High Doses ◽  
Columnar Cells ◽  
Dose Dependent

Local application of retinoic acid to wing buds of chick embryos leads to dose- and position-dependent changes in the pattern of cellular differentiation. Early effects of retinoid treatment on the apical ectodermal ridge coordinate pattern changes and morphogenesis. The length of the apical ridge increases when additional digits will form but decreases when digits are lost. These changes in length can be understood in terms of a threshold response to the local retinoid concentration that results in either disappearance or maintenance of the ridge (Lee & Tickle, J. Embryol. exp. Morph. 90, 139–169 (1985)). Here, we have analysed the mechanisms involved in ridge disappearance by locally applying retinoic acid to the apex of stage 20 chick wing buds. With this treatment regime, low doses give duplicated digit patterns and higher doses truncations. The height of the apical ridge is progressively reduced with increasing doses of retinoid and the time course of ridge flattening indicates that the height of the ridge is correlated with bud outgrowth. With high doses of retinoic acid, the typical ridge, a pseudostratified epithelium in which the columnar cells are tightly packed, disappears and the epithelium at the tip of the bud consists of loosely packed cuboidal cells. Shortly after treatment, there is a decrease in the number of gap junctions between ridge cells. This early change in cell contacts suggests that gap junctions may be involved in maintaining epithelial morphology. When treated epithelium is recombined with untreated mesenchyme, an apical ridge is reestablished and distal structures can be generated. In contrast, when treated mesenchyme is recombined with the epithelium from normal buds, only proximal structures are formed. Therefore, retinoids can lead to a reorganization of the apical ectodermal ridge which is mediated and maintained by the mesenchyme.

Mutant analysis suggests that cyclic GMP mediates the cyclic AMP-induced Ca2+ uptake in Dictyostelium

1991 ◽  
Vol 99 (1) ◽  
pp. 187-191
Author(s):  
S. Menz ◽  
J. Bumann ◽  
E. Jaworski ◽  
D. Malchow
Keyword(s):  
Cyclic Amp ◽  
Mutant Strain ◽  
Cyclic Gmp ◽  
Parental Strain ◽  
Dependent Manner ◽  
Heavy Chains ◽  
Signal Relay ◽  
Sensitive Electrode ◽  
Dose Dependent ◽  
Cyclic Amp Synthesis

Previous work has shown that streamer F (stmF) mutants of Dictyostelium discoideum exhibit prolonged chemotactic elongation in aggregation fields. The mutants carry an altered structural gene for cyclic GMP phosphodiesterase resulting in low activities of this enzyme. Chemotactic stimulation by cyclic AMP causes a rapid transient increase in the cyclic GMP concentration followed by association of myosin heavy chains with the cytoskeleton. Both events persist several times longer in stmF mutants than in the parental strain, indicating that the change in association of myosin with the cytoskeleton is transmitted directly or indirectly by cyclic GMP. We measured the cyclic AMP-induced Ca2+ uptake with a Ca(2+)-sensitive electrode and found that Ca2+ uptake was prolonged in stmF mutants but not in the parental strain. The G alpha 2 mutant strain HC33 (fgdA), devoid of InsP3 release and receptor/guanylate cyclase coupling, lacked Ca2+ uptake. However, the latter response and cyclic GMP formation were normal in the signal-relay mutant strain agip 53 where cyclic AMP-stimulated cyclic AMP synthesis is absent. LiCl, which inhibits InsP3 formation in Dictyostelium, blocked Ca2+ uptake in a dose-dependent manner. The data indicate that the receptor-mediated Ca2+ uptake depends on the InsP3 pathway and is regulated by cyclic GMP. The rate of Ca2+ uptake was correlated in time with the association of myosin with the cytoskeleton, suggesting that Ca2+ uptake is involved in the motility response of the cells.

Intracerebroventricular injection of prostaglandin E2 increases splenic sympathetic nerve activity in rats

1995 ◽  
Vol 269 (3) ◽  
pp. R662-R668 ◽  
Author(s):  
T. Ando ◽  
T. Ichijo ◽  
T. Katafuchi ◽  
T. Hori
Keyword(s):  
Prostaglandin E2 ◽  
Sympathetic Nerve ◽  
Time Course ◽  
Sympathetic Nerve Activity ◽  
Dependent Manner ◽  
Central Administration ◽  
Nerve Activity ◽  
High Doses ◽  
Alpha Chloralose ◽  
Dose Dependent

The effects of central administration of prostaglandin E2 (PGE2) and its selective agonists on splenic sympathetic nerve activity (SNA) were investigated in urethan- and alpha-chloralose-anesthetized rats. An intra-third-cerebroventricular (13V) injection of PGE2 (0.1-10 nmol/kg) increased splenic SNA in a dose-dependent manner. An I3V injection of an EP1 agonist, 17-phenyl-omega-trinor PGE2 (1-30 nmol/kg), also resulted in a dose-dependent increase in splenic SNA, with a time course similar to that of PGE2-induced responses. In contrast, EP2 agonists, butaprost (10-100 nmol/kg I3V) and 11-deoxy-PGE1 (10-100 nmol/kg I3V), had no effect on splenic SNA. An I3V injection of M & B-28767 (an EP3/EP1 agonist, EP3 >> EP1) increased splenic SNA only at high doses (10-100 nmol/kg). Pretreatment with an EP1 antagonist, SC-19220 (200 and 500 nmol/kg), completely blocked the responses of splenic SNA to PGE2 (0.1 nmol/kg) and M & B-28767 (10 nmol/kg), respectively. These findings indicate that brain PGE2 increases splenic SNA through its action on EP1 receptors.

Time- and dose-dependent differential upregulation of three genes by 17β-estradiol in endothelial cells

2002 ◽  
Vol 92 (3) ◽  
pp. 1064-1073 ◽  
Author(s):  
Amparo C. Villablanca ◽  
Kristine A. Lewis ◽  
John C. Rutledge
Keyword(s):  
Endothelial Cells ◽  
Vascular Function ◽  
Time Course ◽  
Plasminogen Activator Inhibitor ◽  
Hormone Treatment ◽  
Plasminogen Activator Inhibitor 1 ◽  
Similar Time ◽  
Differential Display Analysis ◽  
17Β Estradiol ◽  
Dose Dependent

The purpose of this study was to identify genetic targets in the vasculature for estrogen by profiling genes expressed in female human aortic endothelial cells exposed to various doses of 17β-estradiol at differing concentrations and for differing periods of time. Our approach employed a RT-PCR-based cloning strategy of DNA differential display analysis, with differential expression verified by semiquantitative PCR performed with gene-specific primers. A significant increase in mRNA expression in response to 17β-estradiol was observed for the following three genes: aldose reductase (3.4-fold), caspase homologue-α protein (4.2-fold), and plasminogen activator inhibitor-1 intron e (2.3-fold). For all three upregulated genes, estradiol-induced upregulation occurred with a similar time course and temporally clustered to the first 24 h after hormone treatment. In addition, the effect of estradiol dose on gene expression was consistent and occurred at physiological concentrations. Our results describe previously uncharacterized estradiol-sensitive time- and dose-dependent regulation of genes with potential importance to vascular function in human endothelial cells.

scholarly journals Endogenous H2S is required for hypoxic sensing by carotid body glomus cells

2012 ◽  
Vol 303 (9) ◽  
pp. C916-C923 ◽  
Author(s):  
Vladislav V. Makarenko ◽  
Jayasri Nanduri ◽  
Gayatri Raghuraman ◽  
Aaron P. Fox ◽  
Moataz M. Gadalla ◽  
...  
Keyword(s):  
Carotid Body ◽  
Time Course ◽  
Channel Blocker ◽  
Primary Site ◽  
Dependent Manner ◽  
Free Medium ◽  
Adult Rats ◽  
Glomus Cells ◽  
Dose Dependent ◽  
Carotid Body Glomus Cells

H2S generated by the enzyme cystathionine-γ-lyase (CSE) has been implicated in O2 sensing by the carotid body. The objectives of the present study were to determine whether glomus cells, the primary site of hypoxic sensing in the carotid body, generate H2S in an O2-sensitive manner and whether endogenous H2S is required for O2 sensing by glomus cells. Experiments were performed on glomus cells harvested from anesthetized adult rats as well as age and sex-matched CSE+/+ and CSE−/− mice. Physiological levels of hypoxia (Po2 ∼30 mmHg) increased H2S levels in glomus cells, and dl-propargylglycine (PAG), a CSE inhibitor, prevented this response in a dose-dependent manner. Catecholamine (CA) secretion from glomus cells was monitored by carbon-fiber amperometry. Hypoxia increased CA secretion from rat and mouse glomus cells, and this response was markedly attenuated by PAG and in cells from CSE−/− mice. CA secretion evoked by 40 mM KCl, however, was unaffected by PAG or CSE deletion. Exogenous application of a H2S donor (50 μM NaHS) increased cytosolic Ca2+ concentration ([Ca2+]i) in glomus cells, with a time course and magnitude that are similar to that produced by hypoxia. [Ca2+]i responses to NaHS and hypoxia were markedly attenuated in the presence of Ca2+-free medium or cadmium chloride, a pan voltage-gated Ca2+ channel blocker, or nifedipine, an L-type Ca2+ channel inhibitor, suggesting that both hypoxia and H2S share common Ca2+-activating mechanisms. These results demonstrate that H2S generated by CSE is a physiologic mediator of the glomus cell's response to hypoxia.

Cyclic nucleotides, calcium, bicarbonate, and protein secretion in canine pancreatic juice in response to cholecystokinin–pancreozymin

1979 ◽  
Vol 57 (6) ◽  
pp. 541-546 ◽  
Author(s):  
H. L. Cailla ◽  
H. Sarles ◽  
M. V. Singer
Keyword(s):  
Cyclic Amp ◽  
Pancreatic Juice ◽  
Cyclic Gmp ◽  
Cyclic Nucleotides ◽  
Parallel Increase ◽  
Calcium Bicarbonate ◽  
Strong Linear Correlation ◽  
Protein Output ◽  
Dose Dependent ◽  
Stimulation Of

The secretion of cyclic AMP, cyclic GMP, protein, calcium, and bicarbonate in the pancreatic juice of three nonanesthetized dogs with chronic gastric and duodenal Thomas cannulae has been studied. Intravenous infusions of increasing doses of cholecystokinin–pancreozymin (CCK) (1.5, 3, 6, 12, 24 Crick Harper-Raper (CHR) U kg−1 h−1) were administered together with a continuous submaximal dose of secretin (1 clinical unit (CU) kg−1 h−1). Doubling CCK doses every 45 min induced a parallel increase in the output of both cyclic nucleotides. Cyclic AMP output peaked at between 15 and 30 min for 3 and 6 U kg−1 h−1 of CCK and later for 12 and 24 U kg−1 h−1 of CCK whereas cyclic GMP output increased more constantly. Calcium output followed a pattern similar to that of cyclic GMP secretion. Flow rate and protein output attained their peaks at between 30 and 45 min. A strong linear correlation was found between the quantities of cyclic AMP, cyclic GMP, and the quantities of protein secreted in response to each CCK dose. This study demonstrates the presence of cyclic GMP in the canine pancreatic juice and the dose-dependent stimulation of the secretion of cyclic GMP and cyclic AMP by CCK in the presence of secretin.

scholarly journals Interleukin 3-dependent mediator release in basophils triggered by C5a.

1989 ◽  
Vol 170 (2) ◽  
pp. 467-479 ◽  
Author(s):  
Y Kurimoto ◽  
A L de Weck ◽  
C A Dahinden
Keyword(s):  
Time Course ◽  
Lipid Mediators ◽  
Mediator Release ◽  
Lipid Mediator ◽  
Cell Fractionation ◽  
Leukotriene C4 ◽  
Bioactive Lipids ◽  
Anaphylatoxin C5a ◽  
Dose Dependent

The anaphylatoxin C5a is a potent trigger for basophil degranulations, but in contrast to IgE-dependent basophil activation, it does not result in the synthesis of sulfidoleukotrienes (leukotriene C4/D4/E4). Thus, degranulation and the generation of lipid mediators are separately regulated cellular responses. Exposure of human blood basophils to the cytokine IL-3 alone does not induce the release of histamine in cells from most donors and never leads to the generation of LTC4, indicating that IL-3 is not a direct agonist for basophil mediator release. However, preincubation of basophils with IL-3 enhances the degranulation response to C5a. Most importantly, IL-3 "primes" basophils to release large amounts of leukotriene C4 after challenge with C5a (mean of 50 gp LTC4 per nanograms cellular histamine), while neither peptide alone is capable of inducing the formation of bioactive lipids. This effect is dose dependent, occurring at IL-3 concentrations considerably lower than are required to stimulate the growth of bone marrow progenitor cells. IL-3 affects the extent but not the time course of basophil degranulation, and leukotriene release of cells sequentially exposed to IL-3 and C5a occurs very rapidly concomitant with degranulation. A preincubation of the basophils with IL-3 is strictly required for C5a-induced LTC4 synthesis, but not for an enhancement of degranulation. Priming for C5a-induced lipid mediator generation occurs rapidly after exposure of the cells to IL-3, starting at 1 min and reaching maximal effects at 5 min, but this altered state of responsiveness is relatively long lasting. Cell fractionation studies indicate that the basophil is the source of lipid mediators and that IL-3 affects the basophil response directly. This study demonstrates that IL-3 is a potent modifier of effector functions of mature basophils; this is possibly of greater in vivo significance than its growth factor properties. The large amounts of LTC4 formed after triggering of IL-3-primed basophils may not only enhance but also qualitatively change the pathophysiological consequences of complement activation, and this might be important in the pathogenesis of immediate type hypersensitivity reactions, shock syndromes, and inflammation.

Effects of pinacidil on coronary Ca2+-myosin phosphorylation in cold potassium cardioplegia model

2000 ◽  
Vol 279 (3) ◽  
pp. H882-H888 ◽  
Author(s):  
Naruto Matsuda ◽  
Kathleen G. Morgan ◽  
Frank W. Sellke
Keyword(s):  
Time Course ◽  
Dependent Manner ◽  
Coronary Smooth Muscle ◽  
Intracellular Ca ◽  
No Signaling ◽  
Synthase Inhibitor ◽  
Mlc Phosphorylation ◽  
Dose Dependent ◽  
Cardioplegic Solutions

The effects of the potassium (K+) channel opener pinacidil (Pin) on the coronary smooth muscle Ca2+-myosin light chain (MLC) phosphorylation pathway under hypothermic K+cardioplegia were determined by use of an in vitro microvessel model. Rat coronary arterioles (100–260 μm in diameter) were subjected to 60 min of simulated hypothermic (20°C) K+cardioplegic solutions (K+= 25 mM). We first characterized the time course of changes in intracellular Ca2+concentration, MLC phosphorylation, and diameter and observed that the K+cardioplegia-related vasoconstriction was associated with an activation of the Ca2+-MLC phosphorylation pathway. Supplementation with Pin effectively suppressed the Ca2+accumulation and MLC phosphorylation in a dose-dependent manner and subsequently maintained a small decrease in vasomotor tone. The ATP-sensitive K+(KATP)-channel blocker glibenclamide, but not the nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester, significantly inhibited the effect of Pin. K+cardioplegia augments the coronary Ca2+-MLC pathway and results in vasoconstriction. Pin effectively prevents the activation of this pathway and maintains adequate vasorelaxation during K+cardioplegia through a KATP-channel mechanism not coupled with the endothelium-derived NO signaling cascade.

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