Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of the hemicholinium-3 analog, DMAE, on endplate currents (EPC) was investigated in the transected cutaneous pectoris muscle of the frog using a conventional two-microelectrode voltage clamp. At a low concentration (5 microM), DMAE produced a long-lasting decrease in the rate constant of decay (alpha) and an increase in the peak current amplitude (Ip). At higher concentrations (10--100 microM), DMAE produced biphasic changes characterized by a transient, marked decrease of alpha and increase of Ip followed by a long-lasting marked increase of alpha and decrease of Ip. When DMAE was removed from the bath recovery from block was asymmetrical in that alpha recovered more quickly than did Ip. Pretreatment with neostigmine or collagenase partially antagonized the initial effects without affecting the steady state effects of DMAE, indicating that the initial effects of DMAE may be, at least in part, due to inhibition of the enzyme acetylcholinesterase. The drug reverses the normal voltage dependence of alpha without altering the single exponential nature of decay of the EPC. The inward EPC was more markedly blocked than outward EPC, resulting in a highly non-linear current-voltage relation with Ip decreasing with increasing hyperpolarization. This effect may indicate that DMAE causes a voltage-dependent block of closed acetylcholine-activated ion channels.
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PMID:Endplate channel actions of a hemicholinium-3 analog, DMAE. 301 71

A pharmacohistological method was used to study the ultrastructural localization of acetylcholinesterase in the rat striatum. Five hours after administration of an organophosphorous inhibitor (paraoxon), high activities of this enzyme were selectively found in some neurons and at numerous axo-spinous synapses of the asymmetrical type. The cholinergic nature of these synapses appeared unlikely.
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PMID:Localization of acetylcholinesterase activity at synapses of the rat striatum during the stages of recovery after inhibition in vivo. 374 54

The release of transmitters was studied in various structures of the basal ganglia in cats implanted with several push-pull cannulas. Local depolarization enhanced Met-enkephalin release in the globus pallidus. Activation of striatonigral substance P(SP) neutrons stimulated the transmitter release from terminals. Unilateral electrical stimulation of the caudate nucleus evoked GABA release in both substantia nigrae and pallidoentopeduncular nuclei. The unilateral facilitation or interruption of nigral SP transmission modified dopamine (DA) release in the ipsilateral caudate nucleus in contrast, modifications of GABAergic or glycinergic nigral transmissions induced bilateral symmetrical effects, whereas bilateral asymmetrical changes in DA release in the two caudate nuclei were seen during the unilateral modification of nigral DA transmission. Changes in the dendritic release of DA induced changes in serotonin release both in the substantia nigra and in the ipsilateral caudate nucleus. Finally, it will be shown that acetylcholinesterase can be released from the substantia nigra and the caudate nucleus through processes dependent on nerve activity.
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PMID:In vivo release of transmitters in the cat basal ganglia. 616 43

The subnuclear organization of rat interpeduncular nucleus (IPN) has been examined by light microscopy following staining with Nissl and Holmes methods, 3H-leucine autoradiography, acetylcholinesterase (AChE), and cytochrome oxidase histochemistry on plastic sections stained with toluidine blue, and by electron microscopy. Three unpaired and four paired subnuclei are recognized. The rostral subnucleus is heavily stained for AChE, which clearly delineates its borders. It is distinguished ultrastructurally by two types of synapses on dendrites, and two on perikarya. Of the former, one type is formed by presynaptic processes which contain spherical and dense-cored vesicles and make asymmetrical contacts. Dense-cored vesicles are observed in many of the postsynaptic dendrites. A second type has presynaptic processes containing small, pleomorphic vesicles which make symmetrical contacts. Synapses on perikarya are found in the rostral, central, intermediate, lateral, and interstitial subnuclei. The dorsal subnucleus is continuous with the serotonin-containing B8 cells. The central subnucleus is distinguished by longitudinally oriented medial habenular axons separating palisades of cell bodies. These axons, which also traverse the intermediate subnuclei, form en passant S synapses with small dendrites of the central subnucleus. The intermediate subnuclei react faintly for AChE and intensely for cytochrome oxidase. They contain crest synapses formed by two habenular afferents, one from each medial habenula, which contact a narrow dendritic process en passant. The lateral subnuclei react intensely for AChE and have ultrastructural features similar to the rostral subnuclei. The interstitial subnuclei lie within each fasciculus retroflexus as it enters IPN. The small dorsal lateral subnuclei are evident by light microscopy.
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PMID:The subnuclear organization of the rat interpeduncular nucleus: a light and electron microscopic study. 632 69

The stereospecificity of the active center of acetylcholinesterase from human erythrocytes (AChE) and butyrylcholinesterase from horse blood serum (BuChE) in reactions with enantiomers of irreversible organophosphorus inhibitors (OPI) with asymmetrical central phosphorus atom and different structure of the leaving moiety: C2H5O(CH3)P(O)SR, where R = C2H7; C6H13: C4H4SC2H5; C2H4SC2H5 and C2H4S(CH3)C2H5, was studied. The strongest inhibiting effect with respect to cholinesterases was exerted by (-)-isomers of the OPI tested. The differences in the inhibiting activity of (-) and (+)-isomers were especially well-pronounced for OPI with R = C3H7 and C4H4SC2H5. The differences in the inhibiting activity of the enantiomers suggest that the stereospecificity of the active center of AChE was the highest and that of BuChE was considerably lower. After treatment by N,N-dimethyl-2-phenylaziridinium ions which specifically and irreversibly modify the anionic groups on the active surface of AChE, the stereospecificity of the latter is decreased and is approximated to that of BuChE. The differences in stereospecificity of AChE and BuChE are probably due to the considerable differences in the spatial structure of the enzyme active centers.
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PMID:[Stereospecificity of active centers of acylcholinesterases]. 709 83

The fine structure, synaptic relationships, distribution and time of origin of interstitial neurons situated within the white matter subjacent to the visual, somatosensory and motor cortices were studied in the human and monkey telencephalon. The analysis was carried out on Nissl-stained serial sections, rapid Golgi impregnations, by acetylcholinesterase (AChE) histochemistry, electron microscopy and [3H]thymidine ([3H]TdR) autoradiography. Interstitial neurons have a similar distribution, morphology and histochemistry in both human and monkey telencephalon. Their highest density and the most extensive distribution is found in the neonatal period in both species. The number of interstitial neurons decreases during infancy, but numerous cells remain in the adult. Two types of interstitial neuron can be recognized in Golgi preparations: polymorphic cells, usually situated close to the cortex and fusiform cells, located predominantly in the depths of the white matter. The polymorphic cell type is prevalent during neonatal and infant stages, while fusiform cells are relatively more numerous in the adult. Interstitial cells have ultrastructural features and organelles typical of neurons of the central nervous system with well-defined axosomatic and axodendritic synapses of both symmetrical and asymmetrical types. About 20% fo the interstitial cells show strong specific AChE activity. Autoradiographic analysis of postnatal monkeys exposed to [3H]TdR at various embryonic (E) and early postnatal days indicates that interstitial neurons which lie beneath the visual and somatosensory-motor cortices are generated between E38 and E48. Contrary to the prevailing notion that interstitial neurons are the latest generated cells arreste during migration across the maturing white matter, they prove to be produced at the end of the first third of the 165-day gestation in the rhesus monkey concomitantly with the generation of neurons destined for the deep neocortical layers. These findings raise the possibility that interstitial cells represent a vestige of the transient embryonic subplate layer.
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PMID:Cytology and time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. 744 Dec 94

Cholinergic innervation of the cerebral neocortex arises from the basal forebrain and projects to all cortical regions. Acetylcholinesterase (AChE), the enzyme responsible for deactivating acetylcholine, is found within both cholinergic axons arising from the basal forebrain and a subgroup of pyramidal cells in layers III and V of the cerebral cortex. This pattern of staining varies with cortical location and may contribute uniquely to cortical microcircuitry within functionally distinct regions. To explore this issue further, we examined the pattern of AChE staining within auditory, auditory association, and putative language regions of whole, postmortem human brains. The density and distribution of acetylcholine-containing axons and pyramidal cells vary systematically as a function of auditory processing level. Within primary auditory regions AChE-containing axons are dense and pyramidal cells are largely absent. Adjacent cortical regions show a decrease in the density of AChE-containing axons and an increase in AChE-containing pyramidal cells. The posterior auditory and language regions contain a relatively high density of AChE-containing pyramidal cells and AChE-containing axons. Although right and left posterior temporal regions are functionally asymmetrical, there is no apparent asymmetry in the general pattern of AChE staining between homologous regions of the two hemispheres. Thus, the pattern of AChE staining covaries with processing level in the hierarchy of auditory cortical regions, but does not vary between the functionally distinct right and left posterior regions. An asymmetry in the size of layer III AChE-rich pyramidal cells was present within a number of cortical regions. Large AChE-rich pyramidal cells of layer III were consistently greater in size in the left hemisphere as compared to the right. Asymmetry in layer III pyramidal cell size was not restricted to language-associated regions, and could potentially have a variety of etiologies including structural, connectional, and activational differences between the left and right hemisphere.
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PMID:Acetylcholinesterase staining in human auditory and language cortices: regional variation of structural features. 867 Jun 55

The topographical distribution of catecholaminergic nerve fibres and their anatomical relationship to cholinergic elements in the rat globus pallidus were studied. Peroxidase-antiperoxidase and two-colour immunoperoxidase staining procedures were used to demonstrate tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT) and choline acetyltransferase (ChAT) immunoreactivities, combined with acetylcholinesterase (AChE) pharmacohistochemistry. TH immunoreactive nerve fibres were seen to enter the globus pallidus from the medial forebrain bundle. The greatest density of such fibres was found in the ventral region of the globus pallidus, which was also characterized by the greatest density of ChAT immunoreactive neurons. TH immunoreactive nerve fibres showed varicose arborizations and sparse boutons, which were occasionally seen in close opposition to cholinergic structures. In all regions of the globus pallidus, there were also larger, smooth TH immunoreactive nerve fibres of passage to the caudate putamen. A smaller number of DBH immunoreactive nerve fibres and terminal arborizations were found in the substantia innominata, internal capsule and in the globus pallidus bordering these structures. A few PNMT immunoreactive nerve fibres in the substantia innominata and internal capsule did not enter the globus pallidus. Electron microscopy revealed TH immunoreactive synaptic profiles in the ventromedial area of the globus pallidus corresponding to the nucleus basalis magnocellularis of Meynert (nBM). These made mainly symmetrical and only a few asymmetrical synaptic contacts with dendrites containing AChE reaction product. The results indicate that cholinergic structures in the nBM are innervated by dopaminergic fibres and terminals, with only a very small input from noradrenergic fibres.
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PMID:Distribution of catecholaminergic afferent fibres in the rat globus pallidus and their relations with cholinergic neurons. 971 Jan 45

The effect of high electric field in capillary zone electrophoresis (CZE) was evaluated for the study of the thermally induced unfolding of Bungarus fasciatus acetylcholinesterase. This monomer enzyme is characterised by two interdependent uncommon structural features, the asymmetrical distribution of charged residues and a relatively low thermal denaturation temperature. Both traits were presumed to interfere in the thermal unfolding of this enzyme as investigated by CZE. This paper analyses the effect of high electric field on the behaviour of the enzyme native state. It is shown that increasing the applied field causes denaturation-like transition of the enzyme at a current power which does not induce excessive Joule heating in the capillary. The susceptibility to electric field of proteins like cholinesterases, with charge distribution anisotropy, large permanent dipole moment and notable molecular flexibility associated with moderate thermal stability, was subsequently discussed.
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PMID:Dual effect of high electric field in capillary electrophoresis study of the conformational stability of Bungarus fasciatus acetylcholinesterase. 1126 29

The combination of antagonism at histamine H(3) receptors and inhibition of acetylcholinesterase has been recently proposed as an approach to devise putative new therapeutic agents for cognitive diseases. The 4,4'-biphenyl fragment has been reported by us as a rigid scaffold leading to potent and selective non-imidazole H(3)-antagonists. Starting from these premises, the current work presents an expanded series of histamine H(3) receptor antagonists, characterized by a central 4,4'-biphenyl scaffold, where the structure-activity profile of both mono-basic and di-basic compounds is further explored and their ability to inhibit rat brain cholinesterase activity is determined. The steric properties and basicity of the terminal groups were modulated in symmetrical compounds, carrying identical substituents, and in asymmetrical compounds, having a piperidine ring at one end and different groups at the other. The length of the linker connecting the biphenyl scaffold to the terminal groups was also modulated. Binding studies at rat and human H(3) receptors evidenced the highest binding affinities for di-basic compounds, in the order of nM concentrations, and that the steric requirements for the two terminal groups are different. Many potent compounds showed good selectivity profiles over the other histamine receptors. Interestingly, some derivatives displayed a moderate ability to inhibit rat brain cholinesterase, for example compound 12 (1-[2-(4'-piperidinomethyl-biphenyl-4-yl)ethyl]piperidine) has a pIC(50)=5.96 for cholinesterase inhibition and high H(3) receptor binding affinity and antagonist potency (pK(i)=8.70; pK(B)=9.28). These compounds can be considered as rigid analogs of a recently reported class of dual-acting compounds and as a promising starting point for the design of new H(3)-antagonists with anti-cholinesterase activity.
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PMID:Synthesis and structure-activity relationships for biphenyl H3 receptor antagonists with moderate anti-cholinesterase activity. 1897 27


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