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)

Commercially available and affinity-purified butyrylcholinesterases isolated from human serum were examined for their esterasic activity and their ability to hydrolyze various neuropeptides, including neurotensin, substance P, and leucine-enkephalin. The three pools that displayed the lowest esterasic activities were shown to hydrolyze neurotensin with the same HPLC degradative pattern. By contrast, noticeable qualitative and quantitative discrepancies were observed when hydrolyses of substance P and leucine-enkephalin by these three butyrylcholinesterase pools were studied. The pool that exhibited the highest esterasic activity appeared to be homogeneously constituted by 90- and 180-kDa protein bands by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and was totally unable to hydrolyze these three neuropeptides. This suggested that the three other butyrylcholinesterase preparations could be contaminated by exogenous peptidases. This was confirmed by means of three distinct monoclonal antibodies directed toward human serum butyrylcholinesterase. The three IgG-purified fractions precipitated the esterasic activity, whereas they failed to precipitate the neuropeptide-hydrolyzing activities whatever the substrate examined. Altogether, these results demonstrate that peptidases associated with butyrylcholinesterase are contaminating enzymes that cannot be considered as intrinsic activities of this enzyme.
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PMID:Monoclonal antibodies allow precipitation of esterasic but not peptidasic activities associated with butyrylcholinesterase. 169 18

The distribution of specifically-labeled neurotensin binding sites was examined in relation to that of cholinergic neurons in the rat nucleus basalis magnocellularis at both light and electron microscopic levels. Lightly prefixed forebrain slices were either labeled with [125I](Tyr3) neurotensin alone or processed for combined [125I]neurotensin radioautography and acetylcholinesterase histochemistry. In light microscopic radioautographs from 1-microns-thick sections taken from the surface of single-labeled slices, silver grains were found to be preferentially localized over perikarya and proximal processes of nucleus basalis cells. The label was distributed both throughout the cytoplasm and along the plasma membrane of magnocellular neurons all of which were found to be cholinesterase-positive in a double-labeled material. Probability circle analysis of silver grain distribution in electron microscopic radioautographs confirmed that the major fraction (80-89%) of specifically-labeled binding sites associated with cholinesterase-reactive cell bodies and dendrites was intraneuronal. These intraneuronal sites were mainly dispersed throughout the cytoplasm and are thus likely to represent receptors undergoing synthesis, transport and/or recycling. A proportion of the specific label was also localized over the nucleus, suggesting that neurotensin could modulate the expression of acetylcholine-related enzymes in the nucleus basalis. The remainder of the grains (11-20%) were classified as shared, i.e. overlied the plasma membrane of acetylcholinesterase-positive neuronal perikarya and dendrites. Extrapolation from light microscopic data, combined with the observation that shared grains were detected at several contact points along the plasma membrane of cells which also exhibited exclusive grains, made it possible to ascribe these membrane-associated receptors to the cholinergic neurons themselves rather than to abutting cellular profiles. Comparison of grain distribution with the frequency of occurrence of elements directly abutting the plasma membrane of neurotensin-labeled/cholinesterase-positive perikarya indicated that labeled cell surface receptors were more or less evenly distributed along the membrane as opposed to being concentrated opposite abutting axon terminals endowed or not with a visible junctional specialization. The low incidence of labeled binding sites found in close association with abutting axons makes it unlikely that only this sub-population of sites corresponds to functional receptors. On the contrary, the dispersion of labeled receptors seen here along the plasma membrane of cholinergic neurons suggests that neurotensin acts primarily in a paracrine mode to influence the magnocellular cholinergic system in the nucleus basalis.
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PMID:Ultrastructural localization of [125I]neurotensin binding sites to cholinergic neurons of the rat nucleus basalis magnocellularis. 169 63

The distribution of 125I-neurotensin binding sites was compared with that of acetylcholinesterase reactivity in the human basal forebrain by using combined light microscopic radioautography/histochemistry. High 125I-neurotensin binding densities were observed in the bed nucleus of the stria terminalis, islands of Calleja, claustrum, olfactory tubercle, and central nucleus of the amygdala; lower levels were seen in the caudate, putamen, medial septum, diagonal band nucleus, and nucleus basalis of Meynert. Adjacent sections processed for cholinesterase histochemistry demonstrated a regional overlap between the distribution of labeled neurotensin binding sites and that of intense acetylcholinesterase staining in all of the above regions, except in the bed nucleus of the stria terminalis, claustrum, and central amygdaloid nucleus, where dense 125I-neurotensin labeling was detected over areas containing only weak to moderate cholinesterase staining. At higher magnification, 125I-neurotensin-labeled binding sites in the islands of Calleja, supraoptic nucleus of the hypothalamus, medial septum, diagonal band nucleus, and nucleus basalis of Meynert were selectively associated with neuronal perikarya found to be cholinesterase-positive in adjacent sections. Moderate 125I-neurotensin binding was also apparent over the cholinesterase-reactive neuropil of these latter three regions. These data suggest that neurotensin (NT) may directly influence the activity of magnocellular cholinergic neurons in the human basal forebrain, and may be involved in the physiopathology of dementing disorders such as Alzheimer's disease, in which these neurons have been shown to be affected.
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PMID:Distribution of 125I-neurotensin binding sites in human forebrain: comparison with the localization of acetylcholinesterase. 216 57

Neurotensin (NT) is a putative neurotransmitter, the central and peripheral actions of which appear to be mediated by specific high affinity receptors. Recent autoradiographic studies have localized a high proportion of these NT receptors over nerve cell bodies in rat basal forebrain. In the present study, monoiodo-NT-labeled binding sites are shown by combined autoradiography and cholinesterase histochemistry to be selectively associated with cholinergic nerve cell bodies in the diagonal band and substantia innominata of the rat basal forebrain. This finding suggests that endogenous NT may directly influence forebrain cholinergic function in the central nervous system.
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PMID:Selective association of neurotensin receptors with cholinergic neurons in the rat basal forebrain. 283 77

We have previously shown by combined radioautography and acetylcholinesterase histochemistry that the distribution of 125I-neurotensin (NT) binding sites was in register with that of cholinergic neurons in the rat nucleus basalis magnocellularis (NBM). The present study utilized three experimental approaches to elaborate on the type and cellular localization of NT binding sites in the NBM. Competition studies using levocabastine, a selective blocker of the low affinity NT binding component, revealed that most of the 125I-NT binding sites labeled in the NBM are of the levocabastine-insensitive high affinity type, known to correspond to the physiologically active receptor. Ibotenic acid-induced lesions of the NBM produced a marked reduction in both cholinesterase reactivity and cellular 125I-NT binding suggesting that most of the labeled sites are associated with the cholinergic neurons themselves rather than with an afferent input to those cells. Finally, examination of the high resolution radioautographic distribution of 125I-NT binding sites in semithin sections revealed that a proportion of 125I-NT-labeled receptors is associated with the plasma membrane of magnocellular perikarya and proximal processes, thereby providing an anatomical substrate for a local action of NT in the NBM.
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PMID:Anatomical substrate for neurotensin-acetylcholine interactions in the rat basal forebrain. 285 24

Cognitive impairment in schizophrenia occurs in the early phases of the disease and remains throughout its course. The basis for cognition lies in two main brain regions: the prefrontal cortex and hippocampus. Positron emission tomography, functional magnetic resonance imaging, and proton magnetic spectroscopy studies have shown that prefrontal cortex and hippocampus activity and cell density are lower in patients with schizophrenia than in healthy controls. Dopamine remains the fundamental neurotransmitter involved with schizophrenia. Catechol- O -methyltransferase accounts for about 60% of dopamine metabolism in the prefrontal cortex. Functional polymorphism for the catechol- O -methyltransferase genotypes has been identified in patients with schizophrenia. Those with the valine-valine genotype demonstrate rapid inactivation of dopamine, and performance in cognitive testing in patients is poorer with this allele than with other genotypes. N -methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate acid receptors are also strongly associated with cognitive impairment. Changes occur in apolipoproteins D and E, cholinesterase enzyme activity, neurotensin, and neural growth factors, leading to a possible neurodegenerative process and cognitive impairment in patients with schizophrenia. A fundamental link between psychosis and neurocognition probably arises from complex interactions between these systems at the intracellular secondary messenger system and with protein phosphorylation. Atypical antipsychotics evaluated in receptor models, cell cultures, and animal behavior paradigms indicate that these agents may provide neuroprotective effects. Clinical studies with atypical antipsychotics have consistently demonstrated improvement in cognitive symptoms, and such improvement appears to be correlated with improvement of negative symptoms. A neurodevelopmental model of cognitive impairment in schizophrenia aids in understanding why atypical antipsychotics improve cognitive symptoms.
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PMID:Implications for atypical antipsychotics in the treatment of schizophrenia: neurocognition effects and a neuroprotective hypothesis. 1558 43