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)

Sensitivity of the ventral surface of the medulla oblongata to organophosphorus agents, oxime reactivators, and muscarinic antagonists was examined in order to delineate sites of cholinergic activity in the central nervous system. The exposed ventral surface of the medulla oblongata in anaesthetized cats was treated with the organophosphorus anticholinesterase agents soman and (7-nitro-2-oxa-1,3-diazole) aminopentyl methylphosphonofluoridate (NBD-AP-MFP), a fluorescent active centre-selective probe of acetylcholinesterase. Topical application of soman (1-5 micrograms) or NBD-AP-MPF (5-120 micrograms) elicited a profound (80-90 mm Hg), long-lasting (0.5-3 h), dose-dependent vasodepression with only minor changes in heart rate and respiration. The vasodepression was rapidly reversed (7-10 min) upon topical application of muscarinic antagonists (atropine methylnitrate, atropine sulphate) and the bisquaternary oxime HI-6; systemic administration was without effect. Reversal of the hypotension by HI-6 occurred irrespective of whether the organophosphorus agent was NBD-AP-MPF, which forms conjugates with acetylcholinesterase that undergo no aging, or soman, which forms conjugates that undergo extensive aging rendering the enzyme refractory to oxime reactivation. Hence, oxime efficacy for reversal of the physiologic hypotension was not dependent solely on the fraction reactivatable enzyme. By virtue of the fluorescence distribution of NBD-AP-MPF the chemosensitive sites were estimated to reside no deeper than 50 microns into the medulla oblongata, providing a direct indication for localization of the chemosensitive cells on the superficial surface.
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PMID:Target sites for anticholinesterases on the ventral surface of the medulla oblongata: hypotension elicited by organophosphorus agents. 377 92

The rostral ventral surface of medulla oblongata (RVMO) has been shown to constitute a selective target for organophosphate (op) cholinesterase inhibitors. The action of soman (S) as compared with (7-nitrobenz-2-oxa-1,3 diazole)aminopentyl methylphosphonofluoridate (NBD-AP-MPF), a fluorescent organophosphate has now been examined in anesthetized cats pretreated with atropine sulphate. Blood pressure (BP), electrocardiogram (ECG) and respiration (R) were recorded. In some animals a cannula was implanted into the right lateral ventricle. Chemicals were bilaterally applied on RVMO by means of a perspex cannula and removed after 5 min. The application of 2.5 micrograms S or 60 micrograms NBD-AP-MPF elicited severe fall of BP which recovered only after 2 h in the case of the former and up to 45 min in the latter. Smaller doses produced corresponding responses of lesser magnitude. Accompanying R changes consisted in most cases of increased rate and reduced amplitude whereas in others the opposite or mixed alterations occurred. Frequently, sigh-like movements intermingled at periodic intervals with regular R deflections. The sighs were interpreted as aiming to correct blood gases balance. After application of atropine on RVMO--but not by systemic administration--BP and R were restored whereas single repeated i.v. injection of 1 microgram/kg noradrenaline produced only transient reversals without influencing the course of long lasting vasodepression. In contrast, the intraventricular administration of 250-500 micrograms yohimbine considerably reduced both the magnitude and extent of the vasodepression elicited by topically applied organophosphates. It is postulated that central alpha 2-adrenoceptors in contrast to vascular sites are likely involved in the op-induced vasodepression. The present work provides an indication that effective antagonists might be developed considering blockade of these receptors.
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PMID:Yohimbine antagonism of the vasodepression elicited by organophosphates applied on ventral medulla oblongata. 406 84

Awake, unrestrained rats received direct bilateral infusions of the cholinesterase inhibitor, echothiophate, into the dentate gyrus during a 40-min experimental session in a holeboard/activity chamber. Additional animals were similarly tested during intrahippocampal infusions of a novel cholinesterase inhibitor, NBD-AP-MPF. The computerized behavioral pattern monitor recorded the animals' locomotor activity, holepoking, and rearing in a manner that permitted the reconstruction and analysis of their sequential patterns of movement. Both echothiophate and NBD-AP-MPF infusions produced dose-dependent increases in locomotor activity that were accompanied by increased holepoking and rearing. The hyperactivity induced by anticholinesterase infusions was qualitatively similar to the atropine-sensitive effects of infusions of the cholinergic agonist, carbachol, as previously reported. Dye infusions revealed that spread of the infusate was restricted to the dentate gyrus of the anterodorsal hippocampal formation. The locomotor activation caused by the echothiophate infusions into the dentate gyrus were interpreted as indicative of a role for the cholinergic septo-hippocampal pathway in the release of motor responding.
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PMID:Behavior during hippocampal microinfusions: anticholinesterase-induced locomotor activation. 663 38