Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new antiaggregating chemical, alpha-(p-(fluoren-9-ylidenemethyl)phenyl)-2-piperidineethanol (RMI 10,393), designated FYPE, was found to be an effective inhibitor of platelet aggregation induced by adenosine diphosphate (ADP), thrombin, collagen, or epinephrine. Effects of the antiaggregant on platelets were concentration dependent. Aggregation was prevented by low concentrations of FYPE that produced in the platelet only minor ultrastructural changes consisting of loss of microtubules and of discoid shape. Low levels of FYPE that prevented platelet aggregation had no effect on platelet ATPase activities but did alter clot retraction, the thrombin-induced shift in electrophoretic mobility and platelet cholinesterase activity. Market decrease in ADP release and increase in adenyl cyclase activity were produced by low levels of FYPE. This study provides a model for evaluation of platelet antiaggregating compounds in vitro.
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PMID:Effect of a new antiaggregating chemical on the structure and function of the human platelet. 425 15

In this study dosing regimens were designed such that cholinesterase inhibition following exposure to chlorpyrifos was produced in one treatment group, but was absent in the other. The higher dosing regimen inhibited plasma and brain cholinesterase activities by 51 and 70%, respectively, and resulted in decreased [3H]cis-methyldioxolane ([3H]CD) binding, which was attributable to a decrease in Bmax. No concomitant loss of [3H]quinuclidinyl benzilate ([3H]QNB) binding sites was observed, indicating that the M2 muscarinic receptor subtype to which [3H]CD binds is particularly susceptible to alterations induced by chlorpyrifos treatment. As the M2 receptor subtype is surmised to be the muscarinic autoreceptor, decreases in this receptor may exacerbate poisoning by organophosphorus agents as a result of decreased ability to terminate synaptic acetylcholine release. The ability of carbachol to inhibit striatal adenylate cyclase, which is an effector molecule associated with the M2 receptor, was unaltered in chlorpyrifos-treated rats. Decreases in M2 receptors occurred with the higher dosing regimen, in the absence of any clinical manifestations. Thus, in the absence of overt clinical signs, perturbations of the muscarinic receptor system did occur as a result of sub-chronic chlorpyrifos exposure. Such alterations may contribute to neurological impairments that develop following chronic organophosphorus exposure.
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PMID:Effects of sub-chronic in vivo chlorpyrifos exposure on muscarinic receptors and adenylate cyclase of rat striatum. 1175 72

Chronic dichlorvos exposure (6 mg/kg b.wt/day) for a period of 8 weeks resulted in significant reduction in body weight gain of the male Wistar rats. However, the dietary intake remained unchanged in experimental animals following dichlorvos treatment. Activity of the synthesizing enzyme of acetylcholine (ACh) ie, choline acetyltransferase, was found to be significantly increased and the activity of hydrolyzing enzyme, acetyl cholinesterase (AChE), was inhibited in all the three brain regions studied. Chronic dichlorvos treatment also caused significant reduction in both high affinity (HA) and low affinity (LA) choline uptake (CU), with maximal effect being observed in the brain stem followed by cerebellum and cerebrum. Muscarinic receptor binding was significantly decreased in brain stem and cerebellum as reflected in the decreased receptor number (B(max)), without any change in the binding affinity (K(d)) of the receptors. Dichlorvos treatment caused marked inhibition in cAMP synthesis as indicated by decreased adenylate cyclase activity as well as cAMP levels in cerebrum, cerebellum and brain stem. Our study shows that organophosphates may interact with muscarinic receptor-linked second messenger system and this could be a potential mechanism for the neurotoxic effects observed after repeated exposure to low levels of organophosphates, which are unexplainable on the basis of cholinergic hyperactivity.
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PMID:Altered cholinergic metabolism and muscarinic receptor linked second messenger pathways after chronic exposure to dichlorvos in rat brain. 1772 37