Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A propensity for bradycardia in preterm human infants suggested that the heart rate response to cholinergic stimulation may vary during development. Isolated, intact fetal mouse hearts (FMH) in organ culture were used as a model to explore developmental differences in chronotropic response to cholinergic stimulation. FMH's of gestational ages (GA) from 13-22 days, maintained for 36 hr in culture, were exposed to acetylcholine (AcH) with and without prior addition of physostigmine. Heart rate decreased markedly with 10(-4) and 10(-6) M AcH (84 +/- 3 and 48 +/- 4%) in 13-14 day hearts, but the decrease was progressively blunted with increasing age and was only 7 +/- 3 and 3 +/- 2% at 21-22 days GA. Physostigmine markedly enhanced the cholinergic response in older hearts with 54 +/- 4 and 32 +/- 5% decreases in heart rate with the two doses of AcH at 21-22 days. However, it did not alter the response in younger hearts. The data suggest that the chronotropic response to AcH progressively diminishes with advancing GA and the extent of intrinsic cholinesterase activity at different GA's is, in part, responsible for the decrease.
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PMID:Developmental factors contributing to the susceptibility to bradycardia in isolated, cultured fetal mouse hearts. 50 57

Butyryl cholinesterase activity in Glossimetra orientalis was studied histochemically with Gomori's method using butyrylthiocholine as substrate. Eserine sulphate (10(-5) M) was used as inhibitor for AChE. The study reveals that the enzyme is present mainly in the musculature of the reproductive system, excretory canal, nerve cells and fibers, tegument and subtegumentary cells and suckers. The testes, ovary and parenchyma are completely negative. The functional significance of the enzyme in the various locations have been discussed.
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PMID:Histoenzymological compartmentation of butyryl cholinesterase in the Glossimetra orientalis Mehra 1937. 59 93

The distributions of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the superior cervical ganglion (SCG) of the cat were determined by electron microscopy (EM) with the bis-(thioacetoxy)aurate (I), or Au(TA)2, method. Before the infusion of fixative, one of the enzymes was selectively, irreversibly inactivated in vivo, as confirmed by light microscope (LM) examination of sections of the stellate ganglion stained by the more specific copper thiocholine method. Physostigmine-treated controls, for inhibition of AChE or BuChE, were stained concomitantly with tissue for enzyme localization by the Au(TA)2 method for EM examination in each experiment. It was concluded that most of the AChE of the cat SCG is present in the plasma membranes of the preganglionic axons and their terminals, and in the dendritic and perikaryonal plasma membranes of the postsynaptic ganglion cells. BuChE is confined largely to the postsynaptic neuronal plasma membranes. Reasons for the discrepancies between the localizations found by the present direct EM observations and those deduced earlier from LM comparisons of normal and denervated SCG are discussed. It is proposed that a trophic factor released by the preganglionic terminals is probably required for the synthesis of postsynaptic neuronal AChE, and that BuChE may serve as a precursor of AChE at that site.
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PMID:Electron microscope localization of acetylcholinesterase and butyrylcholinesterase in the superior cervical ganglion of the cat. I. Normal ganglion. 70 60

NMR was used to study the binding of acetylcholine, atropine, and physostigmine to acetylcholinesterase. Changes in the linewidth of the N-methyl resonance of acetylcholine, resulting from association with the enzyme during hydrolysis, were utilized to study the enzyme-substrate interaction. Physostigmine inhibited the binding of the substrate while atropine accelerated substrate hydrolysis without interfering with its binding. The dissociation constant, KD and the linewidth of the acetylcholinesterase-inhibitor complex, increment v bound, for atropine and physostigmine can be estimated from the linewidth changes of the N-methyl and phenyl group resonances of atropine and from the N-methyl and C-methyl group resonances of physostigmine resulting from association with the enzyme. The results indicate that there is at least one binding site on the enzyme surface for atropine and one for physostigmine. Further evidence that the two sites are distinct is indicated by the fact that gallamine displaces atropine from its site without competing with physostigmine.
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PMID:Drugs-biomolecule interactions: binding study of substrate and inhibitors to acetylcholinesterase using NMR. 115 40

In chicken hearts, the acetylcholine (ACh) output in response to vagal stimulation was easily detectable by gas chromatography even in the absence of cholinesterase inhibition. Eserine 10(-6) M markedly increased the ACh output. In contrast, the ACh output from the perfused rabbit heart was not measurable in the absence of cholinesterase inhibition. Both ACh concentration and cholinesterase activity were higher in the chicken heart than in the rabbit heart. In conclusion, the isolated perfused chicken heart is at present a unique tool for studying the output of the parasympathetic transmitter in the absence of cholinesterase inhibition.
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PMID:The isolated perfused chicken heart as a tool for studying acetylcholine output in the absence of cholinesterase inhibition. 126 66

Groups of rats were trained in a T-shaped maze to discriminate the effects produced by IP injections of ditran (1.60 mg/kg), either when given singly, or when combined with the acetylcholinesterase inhibitors neostigmine (0.25 mg/kg) or physostigmine (0.50 and 1.00 mg/kg), from the nondrug condition (saline). The results from this state-dependency (StD) model indicated that acquisition of the drug discrimination was similar for the 4 groups of rats. After drug discrimination was established the rats were tested with various drug combinations. Physostigmine (0.50 and 1.00 mg/kg) challenge reversed drug discrimination among rats trained with ditran solely or the ditran plus neostigmine combination. There was no antagonism among the ditran plus physostigmine trained rats. Involvement of the C.N.S. is implicated since tests with neostigmine did not upset ditran discrimination. In addition, survival rate of physostigmine treated mice is increased with ditran. In conclusion, this study indicates the usefulness of employing both training and transfer test procedures when evaluating antagonism in this StD model.
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PMID:Drug discrimination in rats: effects of mixtures of ditran and cholinesterase inhibitors. 126 2

The study of the drugs effective in the treatment of cognitive deficits and memory loss associated with senile dementia of the Alzheimer's type--tacrine and amiridin, acetylcholinesterase inhibitor physostigmine and nootrop piracetam on uptake of 3H-serotonin (3H-5-HT), 3H-adrenaline (3H-AD), 3H-noradrenaline (3H-HA), 2H-dopamine (3H-DA), 3H-gamma-aminobutyric acid (3H-GABA), 3H-glutamic acid (3H-GLU), 3H-aspartic acid (3H-ASP) and 3H-glycine (3H-GLI) showed that tacrine and amiridin (5 x 10(-5) M) statistically significantly (P less than 0.05) inhibited the uptake of 3H-DA and 3H-5-HT. Physostigmine at concentration 5 x 10(-4) M statistically significantly (P less than 0.05) inhibited uptake of 3H-5-HT only. Piracetam at concentration range 1-5 x 10(-3) M had no effect on uptake of all investigated neurotransmitters. The above finding suggest that the uptake of neurotransmitter in nerve terminals is not the main target of amiridin and tacrine.
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PMID:[Effects of amiridin and tacrine, drugs effective in Alzheimer's disease, on synaptosomal uptake of neuromediators]. 135 7

To seek evidence for the involvement of acetylcholinesterase activity in the modulatory influence of the airway epithelium, we examined responses to acetylcholine (ACh), bethanechol, histamine or KCl in isolated epithelium-intact and epithelium-denuded guinea-pig trachealis preparations. The concentration-response curves to ACh were shifted 26-fold to the left by epithelial denudation but the contractile response to KCl was not altered. The response to histamine in epithelium-denuded preparations increased 4-fold with no attenuation in the presence of physostigmine (30 nM). Physostigmine (30 nM) potentiated the response to ACh in epithelium-intact tissues more (about 26-fold) than in epithelium-denuded tissues (about 3.5-fold). Thus, in the presence of physostigmine removing the epithelium had only a slight effect (not statistically significant) on the potency of ACh to contract the trachea. Removing the epithelium had no effect on the potency of bethanechol, a muscarinic receptor agonist that is not a substrate for cholinesterases. Physostigmine itself contracted the trachealis muscle but the pD2 values and maximum responses in epithelium-intact and denuded preparations were not significantly different. The frequency-response curves to electrical field-stimulated cholinergic contractions were unaffected by removing the epithelium. In conclusion, the principal mechanism by which the epithelium inhibits contraction of guinea-pig trachea to exogenously applied ACh is via epithelium-derived acetylcholinesterase activity.
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PMID:Role of acetylcholinesterase in airway epithelium-mediated inhibition of acetylcholine-induced contraction of guinea-pig isolated trachea. 135 49

Molecular forms of acetylcholinesterase were studied in three brain regions from Alzheimer disease patients and non-demented, age-matched controls. In Alzheimer disease patients, the membrane-bound G4 form was decreased in frontal (-71%) and parietal cortex (-45%) and in the caudate-putamen (-47%) from control levels. We also found a decrease of aqueous-soluble acetylcholinesterase molecular forms in the aqueous-soluble acetylcholinesterase molecular forms in the caudate-putamen region. The effect of three clinically significant acetylcholinesterase inhibitors, heptyl-physostigmine, physostigmine and edrophonium, on aqueous-soluble acetylcholinesterase molecular forms of the caudate-putamen was investigated. Heptyl-physostigmine, a physostigmine analogue, showed preferential inhibition for the G1 form. On the contrary, edrophonium inhibited the G4 form more potently than the G1 form. Physostigmine inhibited both forms with similar potency. The clinical implications of selective acetylcholinesterase inhibitors are discussed.
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PMID:Differential inhibition of acetylcholinesterase molecular forms in normal and Alzheimer disease brain. 139 97

The central cardiovascular effects of a cholinesterase inhibitor, physostigmine, were studied in alpha-chloralose- and urethane-anesthetized cats, to determine the underlying site and mechanism of action. Intravenous injection of physostigmine produced a dose-dependent fall in blood pressure and heart rate. These responses were blocked by intravenous injection of atropine; however, the peripheral antimuscarinic agent, methscopolamine, failed to inhibit the depressor response. In decerebrated cats, physostigmine elicited similar responses in blood pressure and heart rate as in intact animals. In spinal cats, physostigmine failed to evoke any response. Physostigmine significantly reduced sympathetic nervous activity, as measured by renal sympathetic nerve discharges, indicating that the fall in blood pressure was due to a decrease in sympathetic tone. These results demonstrate that physostigmine, which crosses the blood-brain barrier, produces a depressor response through stimulation of muscarinic cholinergic receptors, located in the medullary region and that the effect is mediated by a decrease in sympathetic activity.
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PMID:Central cardiovascular effects of physostigmine in anesthetized cats. 143 99


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