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:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The technique of intracerebral dialysis in combination with a sensitive and specific radioenzymatic method was used for recovery and quantification of endogenous extracellular acetylcholine from the striata of freely moving rats. A thin dialysis tube was inserted transversally through the caudate nuclei, and the tube was perfused with Ringer solution, pH 6.1, at a constant rate of 2 microliter min-1. The perfusates were collected at 10-min intervals. In the presence of 1 and 10 microM physostigmine, acetylcholine release was 4.5 +/- 0.02 and 7.3 +/- 0.3 pmol/10 min, respectively (not corrected for recovery). The latter concentration of the acetylcholinesterase inhibitor was used in all experiments. Under basal conditions, acetylcholine output was stable over at least 4 h. A depolarizing K+ concentration produced a sharp, reversible 87% increase in acetylcholine output. Both the basal and K+-stimulated release were Ca2+ dependent. The choline uptake inhibitor hemicholinium-3 (20 micrograms intracerebroventricularly) reduced striatal acetylcholine output to 35% of the basal value within 90 min. Scopolamine (0.34 mg/kg s.c.) provoked a sharp enhancement of acetylcholine release of approximately 63% over basal values, whereas oxotremorine (0.53 mg/kg i.p.) transiently reduced acetylcholine release by 54%. These results indicate the physiological and pharmacological suitability of transstriatal dialysis for monitoring endogenous acetylcholine release.
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PMID:Determination of endogenous acetylcholine release in freely moving rats by transstriatal dialysis coupled to a radioenzymatic assay: effect of drugs. 355 60

The effects of scopolamine on the release of 3H-acetylcholine (ACh) from the guinea-pig myenteric plexus were studied at different stimulation frequencies (0.03-10 Hz) and train lengths (1-180 pulses). Release of 3H-ACh was measured in the absence of cholinesterase inhibitors as the outflow of tritium from myenteric plexus-longitudinal muscle preparations preloaded with 3H-choline. In control experiments the volley output of 3H-ACh declined with increasing train length and increasing stimulation frequency. Stimulation by one pulse produced the highest volley output. Scopolamine facilitated the evoked output of 3H-ACh via blockade of presynaptic muscarine receptors. A significant increase was already observed when the preparation was stimulated with 3 pulses at 10 Hz which indicates that the inhibitory muscarinic mechanism becomes operational within 200 ms. The facilitatory effects of scopolamine depended on both train length and frequency of stimulation. Maximal increases in 3H-ACh output were seen with brief trains (3 and 6 pulses) at a high frequency (10 Hz), or with longer trains (20 and 180 pulses) at lower frequencies (0.3 and 1 Hz). Scopolamine compensated for the frequency-dependent decline of 3H-ACh volley output only during brief periods of stimulation (3 and 6 pulses). It is therefore concluded that the decline in volley output during the first few pulses of a train is due to the negative feedback mechanism which is activated by the transmitter released by the preceding impulses. With longer trains of stimulation the negative feedback mechanism plays only a minor role in regulating the output per pulse.
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PMID:The variation of acetylcholine release from myenteric neurones with stimulation frequency and train length. Role of presynaptic muscarine receptors. 664 41

Scopolamine was either continuously infused or injected once daily into C3H mice. Chronic infusion resulted in mice that were supersensitive to the hypothermia and tremor produced by the muscarinic agonist, oxotremorine. Chronic scopolamine infusion did not alter brain acetylcholinesterase (AChE) or choline acetyltransferase (ChAT) activities but it did produce an increase in brain muscarinic receptors, as measured by quinuclidinyl benzilate (QNB) binding. The maximal increase in QNB binding was seen at the 0.2 mg/kg/hr dose. Further increase in dose resulted in a return to control QNB binding in all brain regions studied except cortex. These animals were still supersensitive to oxotremorine, suggesting a dissociation between receptor number and response to agonist. Animals injected once daily for 10 days with 5 mg/kg exhibited an increase in QNB binding while no increase was seen at 20 mg/kg/day. Chronic oxotremorine infusion resulted in tolerance to the hypothermia-producing effects of oxotremorine. This was accompanied by a decrease in brain QNB binding. Coinfusion of scopolamine with oxotremorine blocked both the tolerance development and receptor changes. These experiments demonstrate that chronic scopolamine treatment can elicit an increase in brain muscarinic receptors which is accompanied by supersensitivity to agonists. However, this effect is not clearly dose related, and a strict relationship between receptor number and agonist response does not exist.
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PMID:Chronic scopolamine treatment and brain cholinergic function. 673 17

Bilateral olfactory bulbectomy produced the increased tendency of mouse-killing behavior in nonkiller rats (60% on the 14th day after surgery). Scopolamine hydrobromide (4 and 8 mg/kg, IP) significantly suppressed the killing response in a dose-dependent manner, whereas methylscopolamine nitrate was ineffective. In order to investigate a possible neural mechanisms, choline acetyltransferase (CAT) and acetylcholinesterase (ACh-E) activities were measured in 7 discrete brain areas: cortex, amygdala, hypothalamus, thalamus, tegmentum, hippocampus, and pons plus medulla oblongata. Although the central anticholinergic drug suppressed mouse-killing, no significant difference in either CAT and ACh-E activities was found between the killer and nonkiller rats in any of the brain areas determined in this study. The evidence suggests that the neurochemical findings may not fit the pharmacological findings for supporting a unified cholinergic hypothesis for mouse-killing behavior.
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PMID:Regional changes in brain cholinergic enzyme activities after bilateral olfactory bulbectomy in relation to mouse-killing behavior by rats. 719 71

1. Habituation was regarded as a difference between exploratory activity measured first (session 1) and that measured second (session 2) in a novel environment. 2. Scopolamine (1.0 mg/kg) significantly increased the horizontal activity in sessions 1 and 2 when administered prior to session 1, resulting in the impairment of habituation. 3. Haloperidol (0.2 mg/kg) inhibited scopolamine-induced hypermotility in session 1, but it did not inhibit the scopolamine-induced impairment of habituation in session 2. 4. The direct cholinergic agonist oxotremorine (0.03 mg/kg), unlike the cholinesterase inhibitor physostigmine, significantly inhibited the scopolamine-induced impairment of habituation in the horizontal and vertical activities. 5. These results suggest that the direct stimulation of cholinergic receptors is more effective for scopolamine-induced amnesia than the indirect stimulation of cholinergic receptors by cholinesterase inhibitors in the habituation task.
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PMID:Characterization of the effects of scopolamine on the habituation of exploratory activity: differential effects of oxotremorine and physostigmine. 792 87

The concentration of acetylcholine (ACh) in rat jejunum that had been homogenized with an ultra-high-speed homogenizer (Biotron) was significantly higher than that in jejunum homogenized with a glass homogenizer. Rats were injected once or repeatedly for 10 days with a muscarinic agonist, pilocarpine (1 mg/kg), or a muscarinic antagonist, scopolamine (5 mg/kg). Animals were killed 20 min or 24 hr after single or consecutive injections, respectively, for determinations of cholinergic activities in the jejunum. Single treatment: Pilocarpine did not cause significant changes in the level of ACh, the activity of acetylcholinesterase (AChE), the binding of [3H]quinuclidinyl benzilate (QNB) or the contractile responses to ACh. Scopolamine reduced the level of ACh and binding of [3H]QNB without inducing significant changes in the activity of AChE and the contractile response. Consecutive treatment: Pilocarpine reduced the binding of [3H]QNB by changing the value of Bmax and reduced the contractile response without affecting the level of ACh or the activity of AChE. Scopolamine increased the binding of [3H]QNB without any effects on the level of ACh, the activity of AChE or the contractile response. In summary, it is possible to determine the level of ACh in a tissue as hard as intestine by homogenization with a Biotron and to assess the cholinergic situation in the intestine of animals that have been poisoned with various agents by estimating cholinergic activities.
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PMID:Complementary improvement of the method for determining cholinergic activities in the small intestine and its application to experiments in vivo. 796 50

The effects of the anticholinesterases tetrahydroaminoacridine (THA) and physostigmine on local cerebral glucose utilization (LCGU) were studied in the conscious rat, using the autoradiographic [14C]deoxyglucose technique. THA (5 mg/kg i.p.) increased LCGU significantly in 8 of the 43 regions studied. A higher dose of THA (10 mg/kg) produced a metabolic activation in 19 of the 43 regions. LCGU increased in cortical areas (including parietal and temporal cortices), the septohippocampal system, the thalamus, the lateral habenula, the basolateral amygdala, the superior colliculus, and the substantia nigra. Scopolamine (4 mg/kg i.p.) reversed the THA-induced LCGU increase. Physostigmine (0.2 and 0.5 mg/kg) increased LCGU in 15 and 22 regions, respectively. The average magnitude of the change induced by 0.5 mg/kg of physostigmine was similar to that observed after THA at 10 mg/kg, but the topography of the effects was somewhat different. Physostigmine increased LCGU in the preoptic magnocellular area, the brainstem, and the cerebellum but not in the parietal cortex. The effects in the septohippocampal system were smaller than those induced by THA. The regional topography of the LCGU increase overlapped the distribution of the M2 muscarinic receptors and that of acetylcholinesterase activity. These data suggest that the major effects of THA and physostigmine on LCGU result from their anticholinesterase action.
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PMID:Tetrahydroaminoacridine and physostigmine increase cerebral glucose utilization in specific cortical and subcortical regions in the rat. 836 Feb 91

1. A class of compounds, 9-aminoacridines, have long been known to be reversible inhibitors of acetylcholinesterase (AChE-EC 3.1.1.7), the most familiar of which is 9-amino-1,2,3,4-tetrahydroacridine (Tacrine). 2. A novel aminoacridine was synthesised: -2-tertiary-butyl-9-amino-1,2,3,4- tetrahydroacridine (2tBuTHA). 3. In vitro comparisons of the acetylcholinesterase inhibitory potential and neurotoxicity compared to Tacrine were performed using a chemically differentiated neuroblastoma cell line (Neuro 2A). 2tBuTHA, but not Tacrine, was cytotoxic to the neural cell following 20 h exposure, despite being the least potent AChE inhibitor (IC80 AChE 12.53 microM +/- 1.14 s.e.m., Neutral Red Uptake IC50 9.53 microM +/- 0.98 s.e.m., MTT Reduction IC80 14.6 microM +/- 1.43 s.e.m.). 4. In vivo studies used a novel application of a five arm radial maze to assess neuropharmacological effects on working memory in control and Scopolamine (1 mg kg-1 i.p.) treated mice. There was an impairment of short term cognitive function with 2tBuTHA (15 mg kg-1 i.p.), but not Tacrine (10 mg kg-1 i.p.) which improved the Scopolamine deficit as expected. 5. This combined in vitro and in vivo data infers a neurotoxic property for the novel compound 2tBuTHA, a close structural analogue of Tacrine.
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PMID:Potential neurotoxicity of a novel aminoacridine analogue. 851 21

Cognitive function of rats treated with saline (control), THA (8 mg/kg, i.p.), scopolamine (5 mg/kg, i.p.), or a combination of THA (8 mg/kg) and scopolamine (5 mg/kg) was tested in the Morris water maze. The latency to find the platform in the water maze was used to evaluate performance. THA did not significantly alter the latency period as compared to control rats. Scopolamine resulted in a highly significant (p<0.01) increase in latency period (183% increase) as compared to saline treated controls. However, when THA was concurrently administered with scopolamine, it was able to completely reverse the performance decrement induced by scopolamine. Immediately following spatial reference memory testing, animals were sacrificed by decapitation one hour post injection. Brains were immediately removed and the cortex, hippocampus, hypothalamus, and pituitary were dissected and their choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity were determined spectrophotometrically. THA administration resulted in a significant increase in ChAT activity in the cortex (23% increase). However, when THA was concurrently administered with scopolamine, a significant increase in ChAT activity was observed in cortex (77% increase), hippocampus (32% increase), hypothalamus (97% increase), and pituitary (92.5% increase). THA administration resulted in a significant decrease in AChE activity (p<0.001) in cortex (62% decrease), hippocampus (78% decrease), and hypothalamus (90% decrease). When tacrine was administered with scopolamine, a significant increase was found in the cortex (197% increase) and the hippocampus (207% increase). In conclusion, the increase in ChAT activity produced by tacrine may in part explain its ability to reverse the scopolamine induced decrease in spatial reference memory and may play a role in its beneficial effect in improving cognitive ability.
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PMID:Effects of tacrine (THA) on spatial reference memory and cholinergic enzymes in specific rat brain regions. 862 10

In vitro studies in hypothalamic-pituitary explants in the rat have suggested cholinergic mediation of arginine vasopressin (AVP) osmoregulation. In this study we attempted to demonstrate, in humans, cholinergic mediation of AVP osmoregulation. Specifically, we tested the hypothesis that the plasma AVP response to an osmolar stimulus would be attenuated by pharmacologic blockade of central nervous system muscarinic or nicotinic receptors in humans. We also evaluated the effects of cholinergic blockade on the norepinephrine (NE) response to an osmolar stimulus. Young normal males underwent hypertonic saline infusion following administration of the centrally active muscarinic antagonist scopolamine or the centrally active nicotinic antagonist mecamylamine. Neither mecamylamine nor scopolamine affected the AVP response to hypertonic saline infusion. Mecamylamine reduced NE concentrations in a dose-dependent manner, but did not affect the slope of the NE increase during hypertonic saline infusion. In a second experiment, we evaluated the effects of scopolamine and mecamylamine on the AVP and NE responses to physostigmine, a cholinesterase inhibitor which stimulates AVP release into plasma through a non-osmolar central nervous system cholinergic mechanism. Scopolamine eliminated the AVP response to physostigmine. Mecamylamine reduced NE concentrations both before and after scopolamine administration but did not affect the slope of the AVP response. These results fail to support cholinergic regulation of the AVP response to osmolar stimulation in humans.
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PMID:Lack of cholinergic regulation of vasopressin and norepinephrine responses to hypertonic saline in humans. 884 15


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