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 nervus terminalis is a ganglionated vertebrate cranial nerve of unknown function that connects the brain and the peripheral nasal structures. To investigate its function, we have studied nervus terminalis ganglion morphology and physiology in the bonnethead shark (Sphyrna tiburo), where the nerve is particularly prominent. Immunocytochemistry for gonadotropin-releasing hormone (GnRH) and Leu-Pro-Leu-Arg-Phe-NH2 (LPLRFamide) revealed two distinct populations of cells. Both were acetylcholinesterase positive, but LPLR-Famide-immunoreactive cells consistently stained more darkly for acetylcholinesterase activity. Tyrosine hydroxylase immunocytochemistry revealed fibers and terminal-like puncta in the ganglion, primarily in areas containing GnRH-immunoreactive cells. Consistent with the anatomy, in vitro electrophysiological recordings provided evidence for cholinergic and catecholaminergic actions. In extracellular recordings, acetylcholine had a variable effect on baseline ganglion cell activity, whereas norepinephrine consistently reduced activity. Electrical stimulation of the nerve trunks suppressed ganglion activity, as did impulses from the brain in vivo. During electrical suppression, acetylcholine consistently increased activity, and norepinephrine decreased activity. Muscarinic and, to a lesser extent, alpha-adrenergic antagonists both increased activity during the electrical suppression, suggesting involvement of both systems. Intracellular recordings revealed two types of ganglion cells that were distinguishable pharmacologically and physiologically. Some cells were hyperpolarized by cholinergic agonists and unaffected by norepinephrine; these cells did not depolarize with peripheral nerve trunk stimulation. Another group of cells did depolarize with peripheral trunk stimulation; a representative of this group was depolarized by carbachol and hyperpolarized by norepinephrine. These and other data suggest that the bonnethead nervus terminalis ganglion contains at least two cell populations that respond differently to acetylcholine and norepinephrine. The bonnethead nervus terminalis ganglion appears to differ fundamentally from sensory and autonomic ganglia but does share some features with the neural circuits of forebrain GnRH systems.
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PMID:Nervus terminalis ganglion of the bonnethead shark (Sphyrna tiburo): evidence for cholinergic and catecholaminergic influence on two cell types distinguished by peptide immunocytochemistry. 770 49

Butyrylcholinesterase (BChE) is a glial cell marker with unknown function. For neuroepithelial cells, BChE has been shown to regulate cell division and expression of the postmitotic marker acetylcholinesterase (AChE), while similar studies are lacking for glial cells. By transducing an antisense-5'BChE cDNA expression vector via calcium phosphate precipitation, we have analyzed the effect of BChE inhibition on proliferation and differentiation of rat oligodendroglia-derived OLN-93 cells. OLN-93 cells were chosen because they are highly proliferative, while expressing markers of differentiated oligodendrocytes (Richter-Landsberg and Heinrich, 1996). First, we established that OLN-93 cells do express BChE protein, albeit chiefly in an inactive state, and that BChE was decreased by antisense-5'BChE transfection. Cell proliferation was also strongly diminished, protein kinase C (PKCalpha) was upregulated, and expression of cytoskeletal and cell surface proteins was altered. In particular, immunoreactivities of the intermediate filament proteins vimentin and the cell adhesion protein F11 were detected, indicating that BChE-inhibited OLN-93 cells have shifted toward an astrocytic phenotype. These data support a role of the glia marker BChE in CNS glial cell proliferation and differentiation, achieved via a nonenzymatic mechanism. The possible biomedical impact of BChE protein, e.g., on CNS nerve regeneration, is briefly discussed.
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PMID:Regulation of the rat oligodendroglia cell line OLN-93 by antisense transfection of butyrylcholinesterase. 1094 Nov 46

Cholinesterases are among the most efficient enzymes known. They are divided into two groups: acetylcholinesterase, involved in the hydrolysis of the neurotransmitter acetylcholine, and butyrylcholinesterase of unknown function. Several crystal structures of the former have shown that the active site is located at the bottom of a deep and narrow gorge, raising the question of how substrate and products enter and leave. Human butyrylcholinesterase (BChE) has attracted attention because it can hydrolyze toxic esters such as cocaine or scavenge organophosphorus pesticides and nerve agents. Here we report the crystal structures of several recombinant truncated human BChE complexes and conjugates and provide a description for mechanistically relevant non-productive substrate and product binding. As expected, the structure of BChE is similar to a previously published theoretical model of this enzyme and to the structure of Torpedo acetylcholinesterase. The main difference between the experimentally determined BChE structure and its model is found at the acyl binding pocket that is significantly bigger than expected. An electron density peak close to the catalytic Ser(198) has been modeled as bound butyrate.
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PMID:Crystal structure of human butyrylcholinesterase and of its complexes with substrate and products. 1286 58

Organophosphorus (OP) insecticides and chemical warfare agents act primarily by inhibiting acetylcholinesterase. There are many secondary targets for OP toxicants as observed for example with the major insecticide chlorpyrifos and its bioactivated metabolite chlorpyrifos oxon (CPO). Therefore, it was surprising that the predominant mouse brain protein labeled in vitro by [(3)H-ethyl]CPO (1 nM) (designated CPO-binding protein or CPO-BP) is not one of these known OP toxicant targets. CPO-BP is a 50-kDa membrane-bound serine hydrolase measured by derivatization with [(3)H]CPO and SDS/PAGE or filtration binding assay. It appears to undergo rapid diethylphosphorylation by [(3)H]CPO followed by either dephosphorylation and reactivation or aging on loss of an ethyl group. CPO and several other OP toxicants potently inhibit CPO-BP in vivo (i.p., 2 h) (50% inhibition at 2-25 mg/kg) and in vitro (50% inhibition at 8-68 nM). Using three chemical labeling reagents, i.e., [(3)H]CPO and the activity-based proteomic probes fluorophosphonate-biotin and fluorophosphonate-rhodamine, mouse brain CPO-BP is identified as serine hydrolase KIAA1363 of unknown function. Brains from KIAA1363(-/-) mice show greatly reduced levels of CPO labeling and hydrolytic metabolism compared to brains from wild-type mice. KIAA1363 therefore is the principal enzyme for metabolizing low levels of CPO in brain and may play a more general role in detoxification of OP nerve poisons.
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PMID:A brain detoxifying enzyme for organophosphorus nerve poisons. 1584 Jul 15

Although the importance of insect saliva in insect-host plant interactions has been acknowledged, there is very limited information on the nature and complexity of the salivary proteome in lepidopteran herbivores. We inspected the labial salivary transcriptome and proteome of Helicoverpa armigera, an important polyphagous pest species. To identify the majority of the salivary proteins we have randomly sequenced 19,389 expressed sequence tags (ESTs) from a normalized cDNA library of salivary glands. In parallel, a non-cytosolic enriched protein fraction was obtained from labial salivary glands and subjected to two-dimensional gel electrophoresis (2-DE) and de novo peptide sequencing. This procedure allowed comparison of peptides and EST sequences and enabled us to identify 65 protein spots from the secreted labial saliva 2DE proteome. The mass spectrometry analysis revealed ecdysone, glucose oxidase, fructosidase, carboxyl/cholinesterase and an uncharacterized protein previously detected in H. armigera midgut proteome. Consistently, their corresponding transcripts are among the most abundant in our cDNA library. We did find redundancy of sequence identification of saliva-secreted proteins suggesting multiple isoforms. As expected, we found several enzymes responsible for digestion and plant offense. In addition, we identified non-digestive proteins such as an arginine kinase and abundant proteins of unknown function. This identification of secreted salivary gland proteins allows a more comprehensive understanding of insect feeding and poses new challenges for the elucidation of protein function.
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PMID:Sialome of a generalist lepidopteran herbivore: identification of transcripts and proteins from Helicoverpa armigera labial salivary glands. 2204 31