Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At the same temperature and with adequate circulation of blood or receptor solution beneath it the permeability of the stratum corneum of the rabbit ear to T2O or to 32P-TPP was the same in vivo as in vitro. When skin permeability was measured in vitro, the subcutaneous adipose tissue present in the full-thickness skin of the rat delayed the penetration of CR, a lipophilic substance with a low water solubility, and decreased the permeability constant by nearly 3x. The retardant solvent PEG 300 did not penetrate the stratum corneum; it formed a hydrogen-bonded complex with the cholinesterase inhibitor VX, thereby reducing the thermodynamic activity and penetration rate of this compound through the stratum corneum. The accelerant solvent DMSO removed protein components from the stratum corneum; electron microscope studies showed that the cells of stratum corneum so treated became separated from one another, and their contents became stainable in bulk with Pb++, indicating the creation of new diffusion pathways. When the temperature, clearance of penetrant from the lower surface of the stratum corneum and penetrant formulation were the same in vivo as in vitro, and the surface of the stratum corneum was saturated with the penetrant or its solution, the results of permeability measurements made in vivo were similar to those made in vitro.
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PMID:Factors affecting the permeability of skin. The relation between in vivo and in vitro observations. 75 61

In summary, the effects of dimethyl sulfoxide (DMSO) and its metabolites, dimethyl sulfone (DMSO2) and dimethyl sulfide (DMS), were studied in five selected systems in rats and mice. DMSO enhanced the taurine excretion and the lethality produced by such aromatic hydrocarbons as benzene and chlorobenzene in rats. In mice, DMSO decreased the toxicity such cholinesterase inhibitors as paraoxon and octamethyl pyrophosphoramide. DMSO also lowered the body temperture of rats and reduced the motor activity of mice. Although DMSO2, the major metabolite of DMSO, was not effective in increasing the lethality of solvent hydrocarbons, it seemed to be quite as effective with respect to the other effects. DMS, although quite potent with respect to lowering body temperature and reducing motor activity, was relatively ineffective otherwise. Thus each of the metabolites has a spectrum of activity different from the parent compound; DMSO has the widest spectrum and DMS the narrowest. It remains to be determined whether the therapeutic effects of DMSO are related to the experimental effects reported above in animals, and whether DMSO2 and DMS may share any of the therapeutic effects of DMSO.
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PMID:Biological effects of the metabolites of dimethyl sulfoxide. 105 34

Genotoxicity of eight topically applied compounds was determined using the bone marrow micronucleus (MN) test and hair follicle nuclear aberration (NA) assay in CD1 mice. Twenty-four hours after a single treatment, cyclophosphamide (CY), applied at doses corresponding to 1/4, 1/8, 1/16, and 1/32 of the published dermal LD50, and N-methyl-N-nitrosourea (MNU), applied at 1/4, 1/8, and 1/16 of the published dermal LD50, were found to increase the incidence of NA in a dose-dependent manner. The frequency of MN was significantly increased only at the highest dose of CY. Using the same protocol, six pesticides applied in dimethyl sulfoxide (DMSO) at doses of 1/8, 1/16, and 1/32 of the dermal LD50 were investigated. Aminocarb and chlordane induced a dose-dependent increase in the frequency of NA, while there was an observed increase in NA incidence at only the highest doses of dichlorvos (DDVP), 4,4'-DDT (DDT), and 2,4-dichlorophenoxyacetic acid (2,4-D). No effect was observed with fenitrothion on nuclear aberrations in hair follicles. Except for the highest dose of chlordane, none of the pesticides tested positive in the bone marrow micronucleus test. Serum cholinesterase levels were reduced to 70 +/- 4.7% of the DMSO control level with DDVP, 57 +/- 8.2% with aminocarb, and 60.3 +/- 4.8% with fenitrothion, indicating some systemic activity with these topically applied agents. The data suggest that aminocarb, chlordane, DDVP, DDT, and 2,4-D are genotoxic as determined by the NA assay and that this assay may be more useful in detecting topically applied genotoxic agents than the more often used bone marrow micronucleus test.
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PMID:Comparison of the activity of topically applied pesticides and the herbicide 2,4-D in two short-term in vivo assays of genotoxicity in the mouse. 208 12

Synaptic transmission in the bullfrog sympathetic ganglion was studied by means of extra- and intracellular recordings. DMSO (3-10%) caused a single orthodromic stimulus to generate a brief burst of repetitive postganglionic discharges. DMSO also partially reversed a preexisting transmission failure in low Ca2+ medium. Ganglia were exposed to gradual reductions in extracellular Ca2+, in the absence and in the presence of DMSO. The recorded amplitude of the postganglionic compound action potential (CAP) was plotted as a function of Ca2+ concentration. In the absence of DMSO transmission failed progressively as Ca2+ was reduced from 1.8 to 0.47 mM but DMSO (3% and 10%) shifted the curve of transmission failure to the left (lower Ca2+ concentration). DMSO inhibits ganglion cholinesterase activity, but this is not the mechanism of its facilitatory effect on Ca2+ entry, since physostigmine did not shift the curve of transmission failure in low Ca2+ to the left. The data suggest that DMSO maintained transmitter release in low Ca2+ by a direct, nonspecific enhancement of Ca2+ influx into the presynaptic nerve terminal.
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PMID:DMSO effects on synaptic facilitation and calcium dependence in bullfrog sympathetic ganglion. 298 96

A wide range of primary pharmacological actions of dimethyl sulfoxide (DMSO) has been documented in laboratory studies: membrane penetration, membrane transport, effects on connective tissue, anti-inflammation, nerve blockade (analgesia), bacteriostasis, diuresis, enhancement or reduction of the effectiveness of other drugs, cholinesterase inhibition, nonspecific enhancement of resistance to infection, vasodilation, muscle relaxation, antagonism to platelet aggregation, and influence on serum cholesterol in experimental hypercholesterolemia. This substance induces differentiation and function of leukemic and other malignant cells. DMSO also has prophylactic radioprotective properties and cryoprotective actions. It protects against ischemic injury.
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PMID:Pharmacology of DMSO. 300 27

1. Dimethyl sulphoxide (DMSO) partially reversed neuromuscular blockade brought about by the action of (+)-tubocurarine or Mg(2+) on the frog sartorius nerve-muscle preparation.2. The amplitude and duration of the endplate potential (e.p.p.) were increased by DMSO at concentrations of 70 mM or greater.3. Miniature endplate potentials were raised in frequency, prolonged in duration and increased in amplitude by DMSO at concentrations of 141 mM or greater, but the increase in amplitude was generally less than in the case of the e.p.p.4. The resting muscle membrane potential was significantly depolarized by DMSO at 70 mM or greater concentrations, both at the endplate and remote from an endplate.5. The reversal of neurmuscular blockade by DMSO can be explained in terms of its previously reported ability to inhibit cholinesterase activity, together with the depolarizing action on muscle.
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PMID:Some effects of dimethyl sulphoxide (DMSO) on the frog neuromuscular junction. 454 49

The heart rate of the isolated, perfused, working rat heart was significantly and equally depressed by 1 X 10(-6)M acetylcholine (ACh) and by 6 X 10(-5)M 4-ketoamyltrimethylammonium (4K), a cholinomimetic agonist. Dimethyl sulfoxide (DMSO) (10 microliter/ml, 140 mM) strongly potentiated the effect of ACh but did not alter the effect of 4K. DMSO (10 microliter/ml, 140 mM) strongly potentiated the effect of ACh but did not alter the effect of 4K. DMSO (10 microliter/ml, 140 mM final concentration) alone had no significant effect upon heart rate when added to the perfusate in incremental additions of 1 microliter X (ml perfusate)-1 X min-1 over a 10-min period. The specific activity of atrial homogenate cholinesterase was 48.8 +/- 3.46 nmoles X min-1 X (mg protein)-1 (mean +/- S.E.M.), 38.2 +/- 1.60 for butyrylcholinesterase, and 11.2 +/- 0.86 for acetylcholinesterase (AChE). True AChE activity (measured in the presence of a maximally effective concentration of tetraisopropylpyrophosphoramide) had a Vmax of 13.4 +/- 0.17 nmoles X min-1 X mg protein)-1 and an apparent Km value of 1 X 10(-4)M acetylthiocholine. At this Km substrate concentration, DMSO inhibited atrial AChE activity (I50 = 9 microliter/ml). At the concentration tested, DMSO inhibited atrial AChE and potentiated ACh effects.
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PMID:Dimethyl sulfoxide: inhibition of acetylcholinesterase in the mammalian heart. 670 58

To resolve the origin(s) of the molecular heterogeneity of human nervous system cholinesterases (ChEs), we used Xenopus oocytes, which produce biologically active ChE when microinjected with unfractionated brain mRNA. The RNA was prepared from primary gliomas, meningiomas and embryonic brain, each of which expresses ChE activity with distinct substrate specificities and molecular forms. Sucrose gradient fractionation of DMSO-denatured mRNA from these sources revealed three size classes of ChE-inducing mRNAs, sedimenting at approximately 32S, 20S and 9S. The amounts of these different classes of ChE-inducing mRNAs varied between the three tissue sources examined. To distinguish between ChEs produced in oocytes and having different substrate specificities, their activity was determined in the presence of selective inhibitors. Both 'true' (acetylcholine hydrolase, EC 3.1.1.7) and 'pseudo' (acylcholine acylhydrolase, EC 3.1.1.8) multimeric cholinesterase activities were found in the mRNA-injected oocytes. Moreover, human brain mRNAs inducing 'true' and 'pseudo' ChE activities had different size distribution, indicating that different mRNAs might be translated into various types of ChEs. These findings imply that the heterogeneity of ChEs in the human nervous system is not limited to the post-translational level, but extends to the level of mRNA.
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PMID:Expression of cholinesterase gene(s) in human brain tissues: translational evidence for multiple mRNA species. 674 36

Anticholinesterase-like effects of dimethylsulfoxide (DMSO) were demonstrated on a variety of invertebrate muscles. The excitatory effects of acetylcholine (ACh) on the isolated preparations of the Geukensia demissa heart and anterior byssus retractor muscle (ABRM), and of the Busycon contrarium radula protractor muscle, were potentiated by DMSO (1-5 microliters/ml; 1 microliter/ml = 14 mM). The negative chronotropic effects of ACh, but not of 4-ketoamyltrimethylammonium, were potentiated by DMSO (1-5 microliters/ml) on the isolated heart of the oyster Crassostrea virginica. These four muscles have acetylcholinesterase enzymes of high activity. In contrast, Mercenaria mercenaria hearts have weak cholinesterase activity, and the effects of ACh on this isolated myocardium were not potentiated by DMSO (2-20 microliters/ml). DMSO (0.1-15 microliters/ml) was a competitive inhibitor of both a crude preparation of oyster heart acetylcholinesterase (AChE) (the Km increased 24-fold with DMSO at 15 microliters/ml; the I50 was 1.3 microliters/ml DMSO when [ACh] = Km) and a purified Electrophorus AChE (the Km increased 4.5-fold when DMSO was 10 microliters/ml; the I50 was 10 microliters/ml DMSO near [ACh] = Km). The same doses of DMSO were needed to potentiate the pharmacological effects of ACh on the oyster heart, as to inhibit the AChE of this tissue.
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PMID:Competitive inhibition by dimethylsulfoxide of molluscan and vertebrate acetylcholinesterase. 683 Jun 11

The effect of dimethyl sulfoxide (DMSO) on the slow ventral root potential, which is related to nociceptive transmission, was investigated in the isolated spinal cord of a newborn rat. DMSO at 0.3-1% (v/v) enhanced the slow ventral root potential, but not mono- and polysynaptic reflex discharges. DMSO at 1% also enhanced the depolarization induced by substance P or capsaicin. In the presence of tetrodotoxin (0.3 microM), DMSO at 1% did not influence the substance P-induced depolarization but enhanced the acetylcholine-induced depolarization. Edrophonium at 10 microM also enhanced the slow ventral root potential, and the magnitude of the effect was comparable to that of 1% DMSO. In the presence of atropine (0.3 microM) and hexamethonium (30 microM), the effect of edrophonium disappeared, but half of the effect of DMSO remained. Artificial cerebrospinal fluid containing either 0.87% (w/v) urea or 4.6% (w/v) sucrose, which has the same osmotic pressure as that containing 1% DMSO, did not have the same effect as DMSO on the slow ventral root potential. In the saphenous nerve-dorsal root preparation, the compound action potential was enhanced by 4-aminopyridine (10 microM), but was not affected by DMSO up to 3%. The results suggest that DMSO enhances the slow ventral root potential through mechanisms based on the inhibition of cholinesterase activity and other action(s) involved in increasing transmitter release from nerve endings in nociceptive transmission pathways in the isolated spinal cord of the newborn rat. Neither the blockade of K+ channels nor hyperosmotic effects are likely mechanisms of DMSO action.
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PMID:Enhancing effect of dimethyl sulfoxide on nociceptive transmission in isolated spinal cord of newborn rat. 968


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