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)

To investigate whether or not pressor responses to repeated stimulation of central cholinoceptive neurons are desensitized, mean arterial blood pressure (MAP) and heart rate (HR) were measured following repeated injections of neostigmine, an acetylcholinesterase inhibitor, into the third cerebral ventricle in conscious, unrestrained intact or adrenalectomized (ADX) rats. Neostigmine (5 x 10(-9) or 5 x 10(-8) mol) in 1 milliliter saline increased MAP dose-dependently and increased HR in intact rats. The peak values in MAP and HR after three repeated injections at 4 hour intervals did not wane. Neostigmine (5 x 10(-8) mol) also increased MAP in ADX rats, and the peak values after the first injection were higher in the ADX rats than in the intact rats. The pressor responses to the second and third injection, however, were less than to the first injection in the ADX rats. HR responses to the repeated injections in the ADX rats were identical to those in the intact rats. These findings suggest that the adrenal gland plays a role in antagonizing the development of desensitization in the neostigmine-induced pressor response.
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PMID:The pressor response induced by repeated injections of neostigmine into the central nervous system is desensitized in adrenalectomized, but not in intact rats. 922 56

To investigate the mutual dependence of calcitonin gene-related peptide (CGRP) and acetylcholine release, we examined the effect of a cholinesterase inhibitor neostigmine on the release of CGRP-like immunoreactivity in rat phrenic nerve-hemidiaphragm muscle preparation, and conversely, the effect of CGRP on [3H]acetylcholine release from motor nerve terminals loaded with [3H]choline in the same preparations of mice. Release of CGRP-like immunoreactivity was increased by electrical nerve stimulation (train of 40 pulses of 200 micros pulse duration and frequency of 50 Hz applied every 10 s) in the whole preparation but not in the segmental preparation containing the endplate region. Neostigmine (0.1-0.3 microM) enhanced the resting release of CGRP-like immunoreactivity in a concentration-dependent manner, whereas it depressed the nerve-evoked release of CGRP-like immunoreactivity. CGRP (1 microM) added to perfusate decreased nerve-evoked [3H]acetylcholine release. These results suggest that CGRP, which is released by electrical nerve stimulation or a cholinesterase inhibitor in intact skeletal muscles, negatively modulates nerve-evoked acetylcholine release.
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PMID:Mutual dependence of calcitonin-gene related peptide and acetylcholine release in neuromuscular preparations. 925 44

The acetylcholinesterase inhibitor neostigmine (2 microg) was microinjected into the lateral cerebral ventricle (i.c.v.) of unanesthetized rats to activate central cholinergic receptors. Changes in arterial blood pressure were correlated with changes in Fos-like immunoreactivity in the hypothalamus and forebrain following cholinergic stimulation. Neostigmine increased mean arterial pressure by 39 +/- 3 mmHg at peak (P < 0.05) from a pretreatment level of 104 +/- 4 mmHg. Blood pressure remained elevated for more than 30 min. Distinct Fos-like immunoreactivity was found in the posterior hypothalamic nucleus, the paraventricular nucleus and the supraoptic nucleus of the hypothalamus, the ventral premamillary nucleus, the central nucleus of amygdala, the lateral septum and the medial preoptic area. In contrast, only a very small amount of Fos-like immunoreactivity was scattered in those regions in a control group injected i.c.v. with saline. Pretreatment with the muscarinic receptor antagonist methylatropine (i.c.v., 0.5 microg) prevented the pressor response to neostigmine and evoked a reduced Fos-like immunoreactivity compared to animals given neostigmine without methylatropine. The pressor response to neostigmine was blocked after pretreatment with phenoxybenzamine, however, this did not prevent the development of Fos-like immunoreactivity. These results indicate that the pressor response induced by central cholinergic stimulation may result from muscarinic receptor activation in specific regions of the hypothalamus and the forebrain that are implicated in regulating cardiovascular activity.
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PMID:Identification of pressor regions activated by central cholinergic stimulation in rat brain. 943 Apr 19

The potency of a series of anticholinesterase (anti-ChE) agents and serotonin-related amines as inhibitors of the aryl acylamidase (AAA) activity associated with electric eel acetylcholinesterase (AChE) (EC 3.1.1.7) and horse serum butyrylcholinesterase (BuChE) (EC 3.1.1.8) was examined and compared with the potency of the same compounds as ChE inhibitors. Neostigmine, physostigmine, BW 284C51, (+/-)-huperzine A, E2020, tacrine, edrophonium and heptyl-physostigmine were, in that order, the most potent in inhibiting eel AChE-associated AAA activity, their inhibitor constant (Ki) values being in the range 0.02-0.37 microM. The rank order of the same compounds as AChE inhibitors basically paralleled that of AAA, although they were in general stronger on AChE (Ki = 0.001-0.05). The peripheral anionic site inhibitors propidium and gallamine were inactive on AChE-associated AAA. Serotonin and its derivatives were slightly stronger on AAA (Ki = 7.5-30 microM) than on AChE (Ki = 20-140 microM). Tacrine (IC50 = 0.03 microM), diisopropylfluorophosphate (IC50 = 0.04 microM), heptyl-physostigmine (IC50 = 0.11 microM), physostigmine (IC50 = 0.15 microM) and tetra-iso-propylpyrophosphoramide (iso-OMPA) (IC50 = 0.75 microM) were the most potent in inhibiting horse serum BuChE-associated AAA activity. Serotonin and related amines were very weak on BuChE-associated AAA activity. These results indicate that the inhibitory potencies of the active site anti-ChE agents on the AAA activity associated with eel AChE and horse serum BuChE are closely correlated with their action on the respective ChE. In addition, the efficacy of tacrine, E2020, heptyl-physostigmine and (+/-)-huperzine A in the treatment of Alzheimer's disease is unlikely to be related to the action of these drugs on ChE-associated AAA.
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PMID:Inhibition of cholinesterase-associated aryl acylamidase activity by anticholinesterase agents: focus on drugs potentially effective in Alzheimer's disease. 963 11

Previous studies have shown that NMDA evokes a calcium-dependent and region-specific increase in extracellular choline that is associated with a reduction of membrane phosphatidylcholine and precedes neuronal cell death. We investigated, using in vivo microdialysis, the contribution of high-affinity choline uptake on the increase in extracellular choline evoked by NMDA. Dialysis was performed in the presence of Neostigmine (0.5 microM), an acetylcholinesterase inhibitor, in prefrontal cortex or hippocampus of freely moving rats. Drugs were administered through the dialysis probe. In cholinergic denervation experiments, rats were subjected to sham or AMPA-induced lesion of cholinergic nuclei at least 2 weeks before microdialysis. Excitotoxic lesion of the medial septum / ventral diagonal band nuclei reduced hippocampal choline acetyltransferase activity by 74%, [(3)H]hemicholinium-3 binding by 32%, and completely abolished potassium-evoked acetylcholine release. Despite this reduction of presynaptic cholinergic function, perfusion of NMDA (300 microM) by retrodialysis produced an increase in hippocampal extracellular choline (249 +/- 22% of basal levels) that was similar to that observed in sham controls (301 +/- 35%). Inhibition of choline uptake with hemicholinium-3 in nonlesioned rats produced a sustained increase in dialysate choline (163 +/- 8%) and reduced acetylcholine to 33 +/- 2% of basal levels, consistent with a depletion of the acetylcholine pool due to precursor deficit. Simultaneous perfusion of hemicholinium-3 and NMDA produced a synergistic increase in dialysate choline (664 +/- 95% of basal levels), indicating that part of the choline released by NMDA is taken up. In contrast, NMDA antagonized the decrease of acetylcholine produced by hemicholinium-3. These results show that NMDA-evoked choline release is not mediated by inhibition of high-affinity choline uptake and indicate that choline released by NMDA can be used to sustain acetylcholine synthesis when there is a precursor deficit secondary to uptake inhibition.
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PMID:Role of high-affinity choline uptake on extracellular choline and acetylcholine evoked by NMDA. 1065 37

The cholinesterase inhibitor neostigmine indirectly stimulates muscarinic M(1)/M(2)/M(3) receptors, thereby reducing colonic distension in acute colonic pseudo-obstruction. We investigated the dose-response profile for the colonic sensorimotor effects of neostigmine and bethanechol, a direct muscarinic M(2)/M(3) agonist in humans. A barostat-manometric assembly recorded phasic pressures, tone, and pressure-volume relationships (compliance) in the descending colon and rectum of 30 healthy subjects who received intravenous neostigmine (0.25, 0.75, or 1.5 mg; n = 15) or subcutaneous bethanechol (2.5, 5, or 10 mg; n = 15). Sensation to luminal distension was also assessed. Thereafter, the effects of neostigmine and bethanechol on colonic transit (geometric center) were compared with those of saline by scintigraphy in 21 subjects. Both drugs increased colonic phasic pressure activity, reduced rectal compliance, and enhanced urgency during rectal distension. Neostigmine also reduced colonic and rectal balloon volumes, reflecting increased tone by an average of 12% and 25% for the highest dose, respectively. Only neostigmine reduced colonic compliance, accelerated colonic transit [mean geometric center at 90 min 2.5 vs. 1.0 (placebo)], and increased pain perception during colonic distension. We conclude that neostigmine has more prominent colonic motor and sensory effects than bethanechol. Moreover, neostigmine induces coordinated colonic propulsion, perhaps by stimulating muscarinic M(1) receptors in the myenteric plexus.
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PMID:Cholinergic stimulation enhances colonic motor activity, transit, and sensation in humans. 1166 32

Neostigmine (cholinesterase inhibitor) or bombesin, when injected into the third cerebral ventricle of awake rat, dose-dependently increased serum glucose with the simultaneous rise in hypothalamic noradrenergic neuronal activity (NAA). Co-administration of octreotide with neostigmine or bombesin suppressed the hypothalamic NNA response with the simultaneous inhibition of the hyperglycemic response. There was a close relationship between hypothalamic NNA and serum glucose in these studies. On the basis of the concept that hypothalamic noradrenergic drive plays an important role in mediating the hyperglycemic response to stressful stimuli, the present findings suggest that the hyperglycemic response to neostigmine or bombesin is mediated via the interaction with hypothalamic noradrenergic neurons.
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PMID:Octreotide-induced suppression of the hyperglycemic response to neostigmine or bombesin: relationship to hypothalamic noradrenergic drive. 1168 73

This study examines the effects of inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) on acetylcholine (ACh)-induced contraction in rat urinary bladder smooth muscle. Neostigmine, a non-selective ChE inhibitor, caused concentration-dependent contractions in rat urinary bladder strips, whereas tetraisopropylpyrophosphoramide (iso-OMPA; a BuChE inhibitor) failed to affect the resting tone of the preparations. Neostigmine (1 microM) markedly augmented the contractile responses to ACh. Although iso-OMPA (10 microM) also potentiated ACh-induced contraction, the effect was less than that evoked by neostigmine. The activities of AChE in rat urinary bladder strips were significantly (P<0.05) higher than those of BuChE. These results indicated that AChE, rather than BuChE, plays an important role in controlling ACh-induced contractions of rat urinary bladder.
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PMID:The role of cholinesterases in rat urinary bladder contractility. 1273 66

Recent studies have suggested that neuroimmune interactions modulate intestinal mucosal immune responses. In the current study, we examined the role of cholinergic pathways in modulating the severity of acute dinitrobenzene sulfonic acid colitis, using pharmacological agents to suppress acetylcholinesterase in Sprague-Dawley rats, and evaluating the colitis in the cholinergic hyperresponsive Flinder's sensitive line rats and their control counterparts, the Flinder's resistant line. Colitis was induced by intrarectal dinitrobenzene sulfonic acid (80 mg x ml(-1) in 50% ethanol); controls received intrarectal saline. Sprague-Dawley rats received an acetylcholinesterase inhibitor, physostigmine (50 microg x kg(-1) s.c.) or neostigmine (50 microg x kg(-1) s.c.), 30 min prior to intrarectal dinitrobenzene sulfonic acid; controls received saline vehicle. On day 5, the macroscopic damage score, myeloperoxidase activity (an estimate of granulocyte infiltration) and smooth muscle thickness were evaluated in the inflamed colonic segment. Significant increases in macroscopic damage score and colonic smooth muscle thickness were observed in Sprague-Dawley and Flinder's Resistant Line rats on day 5 following intrarectal dinitrobenzene sulfonic acid compared to saline controls. Increased myeloperoxidase activity was also observed in dinitrobenzene sulfonic acid-treated Sprague-Dawley rats and Flinder's Resistant Line rats. In contrast, Flinder's Sensitive Line rats failed to demonstrate a significant rise in macroscopic damage, smooth muscle layer thickness, or myeloperoxidase activity on day 5 following intrarectal dinitrobenzene sulfonic acid when compared to saline-treated Flinder's Sensitive Line controls. Neostigmine and physostigmine treatment prior to intrarectal dinitrobenzene sulfonic acid significantly attenuated macroscopic damage score, myeloperoxidase activity and smooth muscle thickness on day 5 compared to colitic Sprague-Dawley controls. Significantly greater reductions in myeloperoxidase activity were observed with physostigmine vs. neostigmine pretreatment. These data suggest that cholinergic pathways modulate the acute colonic inflammatory response associated with the dinitrobenzene sulfonic acid model, with central pathways exerting a greater protective effect relative to peripheral pathways. Further studies are required to determine the contributions of sites in the nervous system and neuro-effector junctions.
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PMID:Cholinergic pathways modulate experimental dinitrobenzene sulfonic acid colitis in rats. 1274 87

Neostigmine injected intra-arterially to the superior cervical ganglion of the cat evoked an asynchronous postganglionic nervous discharge in both normal and denervated superior cervical ganglia. This asynchronous firing was enhanced by tubocurarine but blocked by small doses of atropine. In addition, the responses evoked by acetylcholine in ganglia treated with neostigmine were characterized by two components. The first was blocked by tubocurarine and the second by atropine. Asynchronous firing evoked by repetitive preganglionic nerve stimulation of ganglia treated with neostigmine was blocked by atropine but not tubocurarine. It is suggested that neostigmine (1) has actions on ganglia other than those attributable to inactivation of cholinesterase, (2) may possess both pre- and post-synaptic sites of action, and (3) may unmask a cholinoceptive site which can be blocked by atropine.
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PMID:Asynchronous postganglionic firing from the cat superior cervical sympathetic ganglion treated with neostigmine. 1398 70


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