Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Simple methods were applied to study the teratogenesis in Quail embryos induced by two important organophosphorous compounds: parathion and dicrotophos. Parathion led only to vertebral malformations, as other natural and synthetic cholinomimetics: nicotine, carbamylcholine, decamethonium, neostigmine... Dicrotophos induced not only vertebral malformations (specific to neuromuscular junction poisons) but also beak, legs and feather abnormalities (peripheric malformations which are also produced by insuline and sulfanilamide). Oximes and hydroxamic acids, some of these being analogs of nicotinamide, were tested as antiteratogens. The 3-(CO-NH2), or -(CO-NHOH), substituted pyridinic compounds (nicotinamide, nicotinohydroxamic acid) prevent perfectly dicrotophos-induced beak and legs malformations, in tertiary amine form, but very little in quaternary amine form (methyliodide). The 4-substituted pyridinic compound (isonicotinohydroxamic acid) and aliphatic oxo-oximes were quite ineffecient against these malformations. The vertebral malformations, as a rule, were not lessened by the compounds tested, except for isonicotinoyl-formaldoxime methyl iodide and in some degree for nicotinohydroxamic acid. From these observations, it results that teratogenesis induced by compounds as dicrotophos is rule by a plurificatorial determinism. The beak and legs malformations are prevented by analogs of nicotinamide. In the contrary, the vertebral malformations induced by parathion or dicrotophos are nicotinamide unsensitive and are only prevented by powerful cholinesterase reactivators as pralidoxime or TMB4 (MEINIEL, 1976 b) but are reduced little or not at all by less potent cholinesterase reactivators (HEATH).
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PMID:[On the plurifactorial determinism of the organophosphorous-induced teratogenesis on bird embryos; trials of protection by various compounds: oximes, hydroxamic acids and nicotinamide analogs (author's transl)]. 16 93

Phencylidine derivatives exhibit multiple interactions with cholinergic systems: they block nicotinic and muscarinic receptors,and inhibit both acetyl and butyrylcholinesterase. In peripheral tissue, the net pharmacological effects of the phencyclidines is antiacetylcholine activity. The dissociation constants measured in isolated smooth muscle and from competition experiments for the muscarinic high-affinity binding sites in brain homogenates (Kd = 10(-5) - 10(-6) M) are 3--4 orders of magnitude lower than those of anticholinergic glycolate esters. However, phencyclidines have comparable potency to that of d-tubocurarine in blocking the nicotinic receptor in the isolated frog rectus abdominis (Kd = 10(-6) M). Brain uptake experiments of (3H) labeled phencyclidine showed that during the time period in which central effects are observed with these drugs their concentration in brain reaches values close to the Kd (10(-5) - 10(-6) M). This finding, and the cross tolerance observed in vivo between phencyclidine and other centrally acting cholinergic drugs supports the possible involvement of cholinergic interactions in the psychotropic action of phenyclidine derivatives. Quantum chemical calculations of the interaction pharmacophores of drugs in the phencyclidine series have indicated the molecular determinants for the interaction of these drugs with the muscarinic receptor. The calculations revealed that these drugs can match the reactivity characteristics of ACh and the semi-rigid muscarinic agonist 3-acetoxyquinuclidine, but their rigid molecular frame will be conductive to antagonistic rather than agonistic activity when the drug-receptor complex is formed. The identification of a "cholinergic interaction pharmacophore" for these drugs by quantum mechanical calculations made possible the suggestion of other active phencyclidine derivatives, e.g. p-NH2 and p-OH analogs which proved to be equipotent to phencyclidine. The inactivity of the p-NO2 derivative was also predicted on this basis and served as an additional confirmation of the theoretical criterion for activity; the difference between the activities of the ethynyl and cyano derivatives was explained by the modification of the cholinergic interaction pharmacophore. On the basis of these theoretical predictions, electrophysiological studies were carried out by the others and the results prompted the suggestion that "physostigmine is of potential value in the treatment of post-operative patients emerging from ketamine anesthesia and in the treatment of phencyclidine overdosed patients".
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PMID:Some structure activity relationships of phencyclidine derivatives as anticholinergic agents in vitro and in vivo. 42 35

1. Television pupillometry was used to measure the effect of six topically applied cholinomimetic drugs on the resting diameter and light reflex amplitude of the human pupil. Drug potency was obtained from dose response curves. 2. The tertiary amines arecoline, aceclidine and pilocarpine were considerably more effective miotics than the choline esters carbachol, methacholine and acetylcholine. 3. All the drugs which caused miosis also reduced light reflex amplitude proportionally. 4. The in vitro potency of these drugs was also measured on preparations of rabbit iris sphincter and guinea pig ileum. 5. Dose response relationships for pilocarpine in man and in vitro showed evidence of partial agonist activity on the rabbit iris only. 6. A comparison of the in vivo and in vitro results showed that three factors influenced the potency of topically applied miotics: accessibility to the iris; sensitivity to cholinesterase; and cholinoceptor agonist potency.
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PMID:Factors determining the potency of cholinomimetic miotic drugs and their effect upon the light reflex in man. 67 92

The effect of organic and inorganic forms of nitrogen on biomass accumulation and cholinesterase synthesis was studied with Arthrobacter simplex var. cholinesterasus. The culture assimilates nitrogen of ammonium compounds better than other forms of inorganic nitrogen; the best nitrogen source for biosynthesis of cholinesterase is ammonium phosphate. Nitrogen of nitrates is not assimilated. The amount of biomass is almost twice as high on the medium with peptone, casein or casein hydrolysate as on the medium with mineral nitrogen, while the activity of cholinesterase on these nitrogen sources decreases 1.5--2.0 times. Yeast extract as a nitrogen source increases biomass accumulation by a factor of 2.5 and does not supress synthesis of cholinesterase. The concentration of the enzyme synthesized per unit biomass on the medium with yeast extract is the same as on the medium containing ammonium phosphate. The effect of amino acids and amides, i.e. beta-alanine, proline, amides of aspartic and glutamic acids, and their mixtures, is similar to the action of yeast extract: they stimulate biomass accumulation and do not inhibit synthesis of the enzyme. Other amino acids supress synthesis of cholinesterase. The amount of accumulated biomass in the presence of glutamic acid is twice as high as in the case of any other amino acid, and three times as high as on the medium containing ammonium phosphate. Similar action of glutamic acid is manifested when it is used in mixtures with other amino acids. On the medium containing glutamic acid as a sole source of nitrogen, an increase in biomass production is accompanied with a decrease in biosynthesis of the enzyme by 50%. Repression of the biosynthesis is less if glutamic acid is added in mixtures with proline, beta-alanine and asparagine.
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PMID:[Effect of nitrogen source on growth of Arthrobacter simplex and its biosynthesis of cholinesterase]. 97 79

Light and electron microscopic histochemical reactions were studied in the cells of pars intermedia of the rat. The possible correlations between enzymatic reactions and endocrine functions of these cells were discussed. By combined formaldehyde and chloral vapour treatment the cells of the pars intermedia exhibited a strong yellow fluorescence suggesting the presence of a peptide or peptides with NH2-terminal tryptophan. Masked metachromasia after acid hydrolysis was probably due to these peptides. Only a weak or no alpha-glycerophosphate dehydrogenase and nonspecific esterase activity was observed in the cells of pars intermedia compared to the cells of pars distalis suggesting low production rate of hormone synthesis. Specific and non-specific cholinesterases were demonstrated light and electron microscopically constantly in the cells bordering the lobules. These cells probably represent a certain type of glial cells. In the other cells the enzymatic activities varied markedly in intensity and distribution showing different ultrastructural localizations. Thus cholinesterase activities in the cells of pars intermedia reflect possibly different functional stages of the cells in their hormone production, storage and secretion processes.
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PMID:Observations on the functional cytochemistry of pars intermedia of the rat hypophysis. 124 48

Thyroliberin E-H-P-NH2 (TRH) is a small neuropeptide pGlu-His-Pro-NH2 widely distributed in neural sites. The aim of this work was to obtain an antibody molecule with the nearest properties to that of TRH-receptor in GH3 cells. Different TRH-protein conjugates were prepared and utilized to induce monoclonal antibodies in mice. Several monoclonal antibodies were obtained using E-H-P-NH2 (TRH) coupled either to the histidyl residue (immunogen I) or to the prolyl residue (immunogen II). Antibodies generated using immunogen I and immunogen II were characterized in a radioimmunoassay system and an enzyme immunoassay system respectively. Their selectivities regarding a series of TRH related peptides were compared to those of rabbit polyclonal antibodies using three differently labelled TRH (tritiated-TRH, mono-iodinated-TRH and TRH-OH-acetyl-cholinesterase) as tracers and to prolactin secreting cells TRH receptors using 3H-TRH. Whatever the immunogen, the stereospecificity of monoclonal antibodies tested were found more different from TRH receptor characteristics than rabbit polyclonal antibodies.
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PMID:Properties of monoclonal antibodies to thyroliberin (TRH) induced by different immunogens: comparison with pituitary TRH receptor. 131 25

OBJECTIVE The aim of the study was to investigate whether pyridostigmine, a cholinesterase inhibitor which is thought to act at the hypothalamus to inhibit somatostatin secretion, would augment spontaneous or GHRH-stimulated serum GH levels in patients with GH-insufficiency. DESIGN Oral pyridostigmine 60 mg or placebo was administered at the start of a 9-h subcutaneous infusion of either GHRH (1-29)NH2 10 micrograms/kg/h or saline control. Studies were performed during the daytime (0900-1800 h) in five patients, and the night-time (2100-0600 h) in a further five. PATIENTS Ten short, pre-pubertal children (aged 6-11 years; eight boys) with growth hormone insufficiency were studied. MEASURES Blood for serum GH was sampled every 20 min, and analysed using the PULSAR program. RESULTS The subcutaneous infusion of GHRH 10 micrograms/kg/h increased mean serum GH levels (+/- SEM): by day 17.7(+/- 6.8) vs placebo 2.2(+/- 0.4) mU/l (P less than 0.01), and by night 26.9(+/- 3.3) vs 5.5(+/- 1.3) mU/l (P less than 0.05). There was a significant rise in mean 'baseline' GH concentration: by day 5.5(+/- 1.7) vs 1.0(+/- 0.0) mU/l (P less than 0.05); and night 8.2(+/- 2.7) vs 1.3(+/- 0.3) mU/l (P less than 0.05). Pyridostigmine failed to produce a significant overall increase in either spontaneous or GHRH-stimulated GH secretion by day or night, although there was a significant rise in mean GH levels during the 3 h following pyridostigmine administration in the morning: 4.4(+/- 1.1) vs 2.4(+/- 0.5) mU/l (P less than 0.001). GHRH or pyridostigmine given singly or in combination had no significant effect on the number of pulses. Side-effects attributable to pyridostigmine occurred in seven children. CONCLUSIONS Pyridostigmine, either on its own or as an adjuvant therapy in combination with GHRH, acts for only a brief time and does not offer any potential benefit in the management of children with short stature.
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PMID:Pyridostigmine fails to increase either spontaneous or GHRH-stimulated GH secretion during day or night in growth hormone-insufficient children. 206 Jan 50

The relationship between the lipophilic character of chlorpromazine and seven of its metabolites and their ability to inhibit horse serum cholinesterase (Ki) has been investigated. Log(1/Ki) values were correlated with log P octanol partition coefficients (r = 0.88, P less than 0.01, n = 8). The inhibitor values ranged from 2.7 x 10(-6) M for chlorpromazine to 48.6 x 10(-6) M for monodesmethylchlorpromazine sulphoxide. Ionization constants were determined by limiting solubility, spectrophotometry and pH-partition characteristics. Demethylated metabolites were more basic than the tertiary amines and the sulphoxides were slightly less basic than the corresponding sulphides.
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PMID:Ionization constants, octanol partition coefficients and cholinesterase inhibitor constants for chlorpromazine and its metabolites. 257 50

Piperidine derivatives of hemicholinium-3 were synthesized, which included the following spacing groups between cationic heads: trans-trans-bicyclohexyl, phenanthrene, naphthalene, and biphenyl. Relatively minor structural alterations in these series of compounds resulted in several different types of pharmacological actions related to cholinergic transmission. Structural requirements of the compounds are discussed and include internitrogen distance, structural planarity, spacing groups, and positional isomerism of the quaternary cationic heads. Selected quaternary piperidine derivatives with 14 A inter-atomic distance between the cationic heads exhibit potent HC-3 like activity which is enhanced if a molecule has a nonpolar space filling group (4-methyl piperidine) approximately 3.7 A from the corresponding quaternary cationic head. With selected piperidine ring substitutions, active tertiary amines were also identified. Compounds containing C = O in the spacing moiety were active inhibitors of cholinesterase with some derivatives being nearly as active as physostigmine. When the C = O moiety was reduced to -CH2 and a 2 or 3-CH3 piperidine ring was present, potent non-depolarizing, short acting neuromuscular blocking agents were obtained.
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PMID:Pharmacologic evaluation and structure activity relationships of a series of hemicholinium-3 (HC-3) analogs. 282 40

Monocularly deprived (MD) cats show a loss of responsiveness to visual stimulation of the deprived eye among visual cortical neurons. Several lines of evidence suggest that this effect involves, at least in part, a suppression of deprived eye input, possibly mediated by GABA inhibition. In order to better understand the nature of this suppression we have evaluated the effectiveness of different types of disinhibitory and excitatory agents to reverse the effects of MD. We investigated bicuculline (a GABA antagonist); picrotoxin (a GABA antagonist with a different mechanism of action from bicuculline); strychnine (a glycine antagonist); ammonium ion (a blocker of membrane chloride channels); physostigmine (a cholinesterase inhibitor); and naloxone (an opiate antagonist and also a GABA antagonist). All drugs were given intravenously. Bicuculline restored binocularity to 50% of the visual cortical neurons tested and naloxone to 36%. With both drugs, receptive fields of the normal eye tended to lose specificity. The emergent deprived eye receptive fields were usually similar to those of the normal eye after drug administration. Ammonium ion produced binocular responses in 27% of neurons tested, but receptive fields were grossly abnormal; moreover, ammonium infusion tended to depress neuronal responsiveness. All other drugs tested failed to restore binocularity. These experiments lend further credence to the hypothesis that GABA inhibition contributes to the cortical effects of MD, since only drugs with GABA antagonistic action were effective in restoring neuronal responsiveness to the deprived eye.
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PMID:Comparative pharmacological effects on visual cortical neurons in monocularly deprived cats. 299 1


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