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)

We studied the internal anal sphincter (IAS) muscle from 10 patients with achalasia and five normal controls using histochemical staining for NADPH-diaphorase and acetylcholinesterase (AChE). Normal control IAS muscle contained occasional AChE-positive nerve fibers, whereas IAS achalasia specimens demonstrated prominent AChE-positive nerve fibers in muscle layers. NADPH-diaphorase activity was strongly expressed in nerves in the normal IAS muscle but was absent or scanty in the muscle of patients with IAS achalasia. Our findings of increased AChE-positive nerves and the absence of NADPH-diaphorase activity taken in conjunction with reports of abnormal peptidergic innervation indicate that complex neural abnormalities occur in IAS achalasia. The primary event remains obscure, but it is possible that a single defect, such as nitrergic nerve depletion, may lead to compensatory changes in the other nerve fibers.
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PMID:Absence of NADPH-diaphorase activity in internal anal sphincter (IAS) achalasia. 885 94

Nitric oxide (NO) is synthesized in neurons and is a potent relaxor of vascular and nonvascular smooth muscle. The uterus contains abundant NO-synthesizing nerves which could be autonomic and/or sensory. This study was undertaken to determine: 1) the source(s) of NO-synthesizing nerves in the rat uterus and 2) what other neuropeptides or transmitter markers might coexist with NO in these nerves. Retrograde axonal tracing, utilizing Fluorogold injected into the uterine cervix, was employed for identifying sources of uterine-projecting neurons. NO-synthesizing nerves were visualized by staining for nicotinamide adenine dinucleotide phosphate (reduced)-diaphorase (NADPH-d) and immunostaining with an antibody against neuronal/type I NO synthase (NOS). NADPH-d-positive perikarya and terminal fibers were NOS-immunoreactive (-I). Some NOS-I/NADPH-d-positive nerves in the uterus are parasympathetic and originate from neurons in the pelvic paracervical ganglia (PG) and some are sensory and originate from neurons in thoracic, lumbar, and sacral dorsal root ganglia. No evidence for NOS-I/NADPH-d-positive sympathetic nerves in the uterus was obtained. Furthermore, double immunostaining revealed that in parasympathetic neurons, NOS-I/NADPH-d-reactivity coexists with vasoactive intestinal polypeptide, neuropeptide Y, and acetylcholinesterase and in sensory nerves, NOS-I/NADPH-d-reactivity coexists with calcitonin gene-related peptide and substance P. In addition, tyrosine hydroxylase(TH)-I neurons of the PG do not contain NOS-I/NADPH-d-reactivity, but some TH-I neurons are apposed by NOS-I varicosities. These results suggest NO-synthesizing nerves in the uterus are autonomic and sensory, and could play significant roles, possibly in conjunction with other putative transmitter agents, in the control of uterine myometrium and vasculature.
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PMID:Nitric oxide nerves in the uterus are parasympathetic, sensory, and contain neuropeptides. 753 54

Neurons containing reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase and acetylcholinesterase in the striatum are spared in Huntington's disease. It has been claimed that these neurons are also spared after intrastriatal injection of the N-methyl-D-aspartate receptor agonist, quinolinic acid. In the present study the effects of intrastriatal injection of quinolinic acid (15, 30 and 60 nmol) on neurons containing NADPH diaphorase and acetylcholinesterase were examined in rats. Neurons identified histochemically were counted in whole striatal sections at the level of the injection site and at 400 microns intervals anterior and posterior to the injection site. There was a dose-related reduction in the total number of NADPH diaphorase-containing neurons counted in these levels, but only a mild loss of acetylcholinesterase-containing neurons. Acetylcholinesterase-positive neurons were observed near the injection site following administration of all doses. The effects of the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (50 mg/kg, i.p. twice daily for seven days), on quinolinic acid (30 nmol. day 5)-induced toxicity were also investigated. Striatal sections were stained for NADPH diaphorase-, nitric oxide synthase- and acetylcholinesterase-containing neurons and cells were counted in whole striatal sections at the level of the injection site and at four levels posterior to the injection site. Nitric oxide synthase activity was measured in striatal homogenates. NG-Nitro-L-arginine methyl ester did not protect against or potentiate the loss of NADPH diaphorase-, nitric oxide synthase- or acetylcholinesterase-containing neurons or the loss in nitric oxide synthase activity. Acute intrastriatal injection of quinolinic acid may not be a suitable model for Huntington's disease and a role for nitric oxide in quinolinic acid-induced toxicity is not supported in this model.
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PMID:The effect of nitric oxide synthase inhibition on quinolinic acid toxicity in the rat striatum. 754 92

To characterize the specificity of a novel cholinergic immunotoxin (conjugate of the monoclonal antibody 192IgG against the low-affinity nerve growth factor receptor with the cytotoxic protein saporin), coronal sections through the basal forebrain of adult rats, that received a single intracerebro-ventricular injection of 4 micrograms of 192IgG-saporin conjugate, were subjected to histochemical and immunocytochemical procedures to evaluate cholinergic (choline acetyltransferase (ChAT)-immunoreactive, acetylcholinesterase-positive, NADPH-diaphorase-positive) and GABAergic structures (parvalbumin-immunoreactive, labeling of perineuronal nets with Wisteria floribunda agglutinin) as well as microglia (visualized with Griffonia simplicifolia agglutinin) and astrocytes (immunostaining for glial fibrillary acidic protein). Seven days following injection of the immunotoxin, ChAT-immunoreactive cells nearly completely disappeared throughout the magnocellular basal forebrain complex, including globus pallidus, as compared to vehicle-injected controls. However, there was no significant difference in the number of ChAT-positive cells in the adjacent ventral pallidum and in the caudate-putamen of immunolesioned and control animals. NADPH-diaphorase-containing cells, including a significant subpopulation of cholinergic cells, also strikingly decreased in number by more than 90% in the magnocellular basal forebrain complex following immunolesion, and only a few noncholinergic diaphorase-positive cells survived in the medial septum, vertical and horizontal diagonal band, and nucleus basalis of Meynert. In contrast, the number of parvalbumin-containing GABAergic projection neurons in the septum-diagonal band of Broca complex and nucleus basalis of Meynert from immunolesioned rats was not different from that of vehicle-injected control animals. Immunolesioning also did not result in any change in either number or shape of cells surrounded by perineuronal nets, which are frequently associated with parvalbumin-containing GABAergic neurons. Seven days following injection of the immunotoxin, a very strong activation of microglia with an identical distribution pattern was observed in all experimental animals. Large numbers of activated microglia were found in all magnocellular basal forebrain nuclei, corresponding to the distribution of degenerating cholinergic cells. Additionally, immunolesioning also resulted in a dramatic activation of microglia in the lateral septal nuclei, which are known to be almost free of cholinergic cells, but not of penetrating cholinergic dendrites in adjacent zones, and in the ventral pallidum, where there was no observed loss of cholinergic cells. There was no significant increase in microglia activation in striatum and cortical areas, and no astrocytic response in any of the basal forebrain nuclei at this particular time point of survival. These results suggest that 192IgG-saporin specifically destroys basal forebrain cholinergic neurons and does not suppress their neuronal activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:192IgG-saporin immunotoxin-induced loss of cholinergic cells differentially activates microglia in rat basal forebrain nuclei. 756 26

The localization of nitric oxide synthase, the enzyme responsible for producing the short-acting messenger nitric oxide, has been determined in the digestive tract of the rat using histochemistry for reduced nicotinamide adenine dinucleotide phosphate-diaphorase activity, a specific marker for neuronal nitric oxide synthase. Positively stained neurons were found throughout the entire digestive tract from the esophagus to the rectum. Positive neuronal somata were very common in the myenteric ganglia. Dense positive fibers were distributed in internodal strands, the secondary plexus, the tertiary plexus, and were particularly abundant in the deep muscular plexus, while very few were observed in the submucosal ganglia. The density of these positive structures was higher in the small and large intestine than in the esophagus and stomach. The pattern of distribution suggested that some of these positive cells innervate gut muscles. Double-staining revealed that in these enteric neurons, nitric oxide synthase does not co-localize with acetylcholinesterase. Instead, vasoactive intestinal polypeptide almost always coexists with nitric oxide synthase in the myenteric plexus. Thus, nitric oxide and vasoactive intestinal polypeptide may be co-transmitters in a population of non-adrenergic, non-cholinergic neurons in the enteric nervous system.
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PMID:Histochemical localization of nitric oxide synthase in rat enteric nervous system. 768 13

1. NG-monomethyl-L-arginine (L-NMMA, a nitric oxide synthase inhibitor) inhibits vasodilator responses to acetylcholine but not methacholine in human forearm vasculature. To investigate whether this difference results from the relative susceptibility of these agonists to hydrolysis by acetylcholinesterase, we studied vasodilator responses to brachial artery administration of acetylcholine alone and in the presence of the acetylcholinesterase inhibitor edrophonium. 2. Vasodilator responses to constant-rate brachial artery infusions of acetylcholine were biphasic, with an initial peak response fading over 2 min to a plateau. Fade [(peak-plateau)/peak x 100%] was dose dependent (P < 0.02), ranging from 43 +/- 7% (mean +/- SEM) at low dose (16 nmol/min) to 9 +/- 8% at high dose (83 nmol/min). 3. Edrophonium (0.5 mumol/min intra-arterially) alone produced no change in forearm blood flow but increased blood flow responses to acetylcholine (P < 0.01), causing an approximately 10-fold reduction in the dose required to increase plateau blood flow by 10 ml min-1 100 ml-1. 4. Responses to low doses of acetylcholine alone (16 and 41 nmol/min) faded more (P < 0.01) than those to doses of acetylcholine with edrophonium chosen to produce similar plateau blood flows. Responses to acetylcholine (41 nmol/min) also faded more (P < 0.01) than those to methacholine (5 nmol/min), producing matched plateau flows. 5. Peak and plateau responses to acetylcholine (41 nmol/min) were reduced (P < 0.01) by similar amounts (47 +/- 15%, and 37 +/- 13% respectively, P = 0.39) by coinfusion of L/NMMA (4 mumol/min).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of acetylcholinesterase selectively potentiates NG-monomethyl-L-arginine-resistant actions of acetylcholine in human forearm vasculature. 770 91

Using acetylcholinesterase (AChE), nicotinamide adenine dinucleotide diaphorase (NADHd), and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) enzyme histochemical techniques, the ganglionated plexuses of the porcine enteric nervous system were investigated in small intestine whole-mount preparations. Both AchE and NADHd techniques revealed a majority of the neurons in the ganglia of all three major plexuses. The AchE technique also demonstrated clearly the axodendritic networks of the plexus myentericus. Intraganglionic blank areas revealed the localization of negative cell groups. A very high correlation was found between the activity of both enzymes in one neuron, although this correlation was certainly not linear. Many neurons exhibited a stronger signal for one enzyme. A very small part of the positive nerve cells showed intense staining for both AchE and NADHd. The NADPHd technique demonstrated that the NADPHd-positive neurons fill the negative intraganglionic spaces in the ganglia. Double staining with the two other enzymes showed virtually no colocalization of NADPHd with either NADHd or AchE in the porcine jejunal enteric ganglia. Little negative intraganglionic spaces were seldom found, leaving room for perhaps still more negative enteric neurons. Based upon these results we suggest that the enteric neurons of the porcine small intestine can be subdivided into AchE-NADHd and NADPHd subpopulations. Since the latter colocalizes with the neuronal NO synthase enzyme, we further suggest a subdivision of the enteric nerve cells into AchE-NADHd and NOS-NADHd neurons.
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PMID:Classification of the enteric nerve cells of the porcine small intestine into two subpopulations using enzyme histochemical techniques. 781 33

The aim of this study was to determine to what extent the neuronal phenotypes present in primary cultures of rat striatal neurones correspond to those present in vivo. A large percentage of cultured striatal neurones contained relatively high levels of proenkephalin mRNA. In addition, a high level of expression was found for the prosomatostatin mRNA. Protachykinin mRNA and proneuropeptide Y mRNA were also expressed, but at a comparatively low level. No prodynorphin mRNA could be detected. Considerable numbers of neurones were also found to express NADPH-diaphorase activity, while a smaller number of neurones were positive for acetylcholinesterase. The NADPH-diaphorase and the acetylcholinesterase could be detected both in cell bodies, and in neuronal processes contacting groups of neighbouring neurones. Since nitric oxide does not require synaptic specialisations to exert its intercellular actions, this provides strong evidence that NADPH-positive neurones communicate with other cells in primary culture. These observations demonstrate that when striatal neurones are grown in primary culture, a range of neurochemical phenotypes are present which correspond closely to those present in the mature striatum in vivo. Together with the evidence for cell-cell interactions, this suggests that primary striatal cultures will provide a suitable model to study the molecular mechanisms controlling striatal function.
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PMID:Phenotypic characterisation of rat striatal neurones in primary culture. 788 79

Neurons in the hypogastric (main pelvic) ganglia of 4- and 24-month-old male rats were investigated by enzyme histochemical methods for NADPH-diaphorase (NADPH-d) and acetylcholinesterase (AChE) activities and by immunofluorescence for tyrosine hydroxylase (TH) and neuropeptide Y (NPY) immunoreactivities. Systematic random sampling of standard sized areas of ganglion parenchyma revealed a content (per unit area) of 40.9 +/- 8.41 NADPH-d-positive neurons and 14.42 +/- 6.7 intensely AChE-positive neurons. In the aged rats the staining intensity was unchanged, but reductions in the numbers of cells stained for NADPH-d and AChE were not significantly different. Similar counts of TH- and NPY-immunoreactive neurons revealed values of 23.2 +/- 1.77 and 19.94 +/- 4.9, respectively, suggesting frequent co-localisation. The numbers of TH- and NPY-immunoreactive neurons were found to have decreased with age by 53% and 60%, respectively. Staining of consecutive sections revealed that those neurons which stained positively for NADPH-d did not show immunoreactivity for TH or NPY, and those neurons that were immunoreactive for TH or NPY did not contain intense NADPH-d staining. Occasional NPY-1R neurons were both TH- and NADPH-d-negative. These results suggest that NADPH-d staining is predominantly confined to the parasympathetic neuron population of the hypogastric ganglion and that it is the sympathetic neuron population alone that decreases in number with age.
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PMID:Localisation of NADPH-diaphorase and acetylcholinesterase activities and of tyrosine hydroxylase and neuropeptide-Y immunoreactivity in neurons of the hypogastric ganglion of young adult and aged rats. 790 77

The Stone maze paradigm has been developed for use as a rat model of memory impairment observed in normal aging and in Alzheimer's disease. Results from several studies have demonstrated the involvement of both cholinergic and glutamatergic systems in acquisition performance in this complex maze task. Although results of clinical studies on the cognitive enhancing abilities of cholinomimetics for treatment of memory impairment in Alzheimer's disease have been inconsistent, new classes of cholinesterase inhibitors offer greater potential for therapeutic efficacy. The physostigimine derivative, phenserine, appears to have marked efficacy for improving learning performance of aged rats or of young rats treated with scopolamine in the Stone maze. Declines in markers of glutamatergic neurotransmission in Alzheimer's disease and in normal aging suggest that pharmacological manipulation of this system might also prove beneficial for cognitive enhancement. Treatment with glycine and/or polyamine agonists is suggested as a strategy for activating the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. In addition, the use of combined pharmacological activation of cholinergic and glutamatergic systems is suggested. Manipulation of signal transduction events should also be considered as a strategy for cognitive enhancement. The influx of Ca2+ through the channel formed by the NMDA receptor stimulates the production of the oxyradical, nitric oxide (NO*), via the action of nitric oxide synthase (NOS). Compounds that inhibit NOS activity impair acquisition in the Stone maze, suggesting an involvement of NO*. Thus, strategies for inducing NO* production to enhance cognitive performance may be beneficial. Because of the potential neurotoxicity for NO*, this strategy is not straightforward. Although many new directions beyond the cholinergic hypothesis can be suggested, each has its potential benefits which must be weighed against its risks. Nonetheless, an important unifying area for neurobiological research examining mechanisms of normal brain aging and of age-related neuropathology, as observed in Alzheimer's disease, might emerge from the identification of NO* as a simple molecule serving vital physiological functions but representing potential for neurotoxicity.
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PMID:Rodent models of memory dysfunction in Alzheimer's disease and normal aging: moving beyond the cholinergic hypothesis. 799 63


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