Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

1. The carotid body and the carotid nerve were removed from anaesthetized cats and placed in a small Perspex channel through which Locke solution (at various pH values and usually equilibrated with 50% O(2) in N(2)) was allowed to flow. The glomus was immersed in the flowing solution while the nerve was lifted into oil covering the saline. Sensory discharges were recorded from the nerve and their frequency was used as an index of receptor activity. At times, a small segment of carotid artery, containing pressoreceptor endings, was removed together with the glomus. In this case, pressoreceptor discharges were recorded from the nerve.2. The amplitude of either chemo- or pressoreceptor discharges was not changed by strong acid solutions. Acid decreased the frequency of the baroreceptor discharges only when pH fell to less than 4.0. Solutions at low pH increased the chemosensory discharge, but acid depressed the increased chemoreceptor discharge elicited by KCl. These experiments indicated that H(+) ions probably acted as membrane ;stabilizers' without depolarizing either the nerve fibres or endings.3. Acid solutions increased the action of acetylcholine chloride (AChCl) (100-200 mug) on chemoreceptors. This effect probably was due either to inactivation of tissue cholinesterase or to enhanced sensitivity of the sensory endings to ACh.4. Choline chloride (10(-3)M), which favours ACh synthesis, protected the preparation against decay during prolonged experimentation. Hemicholinium-3 (HC-3), which blocks ACh synthesis in low concentrations (10(-5)M), depressed the chemosensory response to acid and to hypoxia when such stimuli were applied repeatedly. This concentration of HC-3 did not change effects of applied ACh.5. Substances which affect ACh release markedly changed the chemoreceptor discharge increase induced by acidity and other forms of stimulation. In the absence of Ca(2+), acid, anoxia, and interruption of flow provoked receptor depression while receptor excitation induced by ACh and KCl persisted. All stimuli excited and showed increased effectiveness as the Ca(2+) concentration was raised, but their effects declined as Ca(2+) was increased above normal values. Mg(2+) ions depressed the chemoreceptor effects induced by all these stimuli. The action of Mg(2+) was not due entirely to nerve ending block. Morphine sulphate (which decreases ACh release in other structures) also depressed the receptor response to acid and flow interruption.6. Cholinergic blocking agents such as mecamylamine, hexamethonium, atropine, dihydro-beta-erithroidine (DHE), HC-3 (10(-4)M), choline and acetylcholine (in combination with choline) depressed the effects of acid and ACh on the chemoreceptors. The effect induced by interruption of flow was depressed only by mecamylamine and DHE.7. Agents which affect the fate of released ACh, such as acetylcholinesterase and eserine salicylate, did not affect clearly the response of chemoreceptors to acid.8. The results suggest that acid stimulates chemoreceptor fibres through an indirect mechanism, viz. through increased release and/or decreased destruction of a presynaptic transmitter from the glomus cell. This transmitter is probably ACh (see following paper, Eyzaguirre & Zapata, 1968).
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PMID:Pharmacology of pH effects on carotid body chemoreceptors in vitro. 429 75

1. Contractions of the isolated taenia of the guinea-pig caecum produced by acetylcholine and TMA were examined in the presence of various antagonists and anticholinesterases.2. Hemicholinium-3 (HC-3) (50-400 mug/ml) inhibited contractions or relaxations produced by TMA but not contractions produced by acetylcholine. The inhibition was rapid in onset and readily reversible. Contractions produced by transmural stimulation were unaffected by HC-3 but responses produced by nicotine were inhibited.3. Low concentrations of hyoscine and benzhexol inhibited responses to acetylcholine to a greater extent than those to TMA.4. Morphine, raised concentrations of Mg(++) or reduced concentrations of Ca(++) inhibited contractions produced by TMA and by acetylcholine to a similar extent.5. Edrophonium, in concentrations which preferentially inhibit acetylcholinesterase, increased contractions produced by acetylcholine and converted responses to nicotine or transmural stimulation into contractions or biphasic responses with a marked contraction phase but did not increase contractions produced by TMA.6. Iso-OMPA, in concentrations which preferentially inhibit butyrylcholinesterase, had no effect on responses to acetylcholine, nicotine, transmural stimulation or TMA.7. HC-3 inhibited contractions produced by TMA in the presence of anticholinesterases but had little effect on contractions produced by acetylcholine.8. These results suggest that TMA produces contractions by acting directly on receptors of the smooth muscle. An analysis of possible reasons for HC-3 (in the concentrations used) acting as an antagonist of TMA but not of acetylcholine indicates that the findings do not necessarily contradict the interpretation that both agonists act on the same receptor.
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PMID:Differentiation between the actions of acetylcholine and tetramethylammonium on the isolated taenia of the guinea-pig caecum by hemicholinium-3. 432 8

Latency to vocalization and jump/flinch behaviors were scored as the nociceptive endpoints in mice in a grid-shock apparatus that delivered increasing shock levels through a grid floor. Morphine produced a dose-dependent increase in latency to vocalization and was equieffective at a 70- or 80-dB vocalization level. The jump/flinch behavior was not dose dependently modified by morphine. The mouse grid-shock procedure was pharmacologically characterized by using the 70-dB level endpoint. The antinociceptive potencies of the mu opioid receptor agonist analgesics, morphine, methadone, fentanyl, oxycodone, meperidine, etorphine and codeine, correlated well (R = .989) with their clinical doses. The mixed opioid agonist-antagonist, pentazocine, and the partial mu receptor opioid agonist, buprenorphine, were partially effective. The alpha-2 adrenergic agonists clonidine and flupirtine and the serotonergic 5-HT1B agonists 1-(m-trifluoromethyl)piperazine and anpirtoline, were all effective antinociceptives with potencies 20 times less to one-half that of morphine. The gamma-aminobutyric acid agonist 4,5,6,7-tetrahydroisoxazolo[5,4- c]pyridin-3(2H)-one was partially effective, whereas the gamma-aminobutyric acid uptake inhibitors SKF 100300A [N-(4,4-diphenyl-3-butenyl)-guvacine] and tiagabine were highly effective and 6 and 2 times less potent than morphine, respectively. The muscarinic agonists, oxotremorine and arecoline, and the cholinesterase inhibitor, physostigmine, were also antinociceptive, ranging from 7 times less to 100 times more potent than morphine. The nonsteroidal anti-inflammatory analgesic, aspirin, was inactive. The present studies show that the latency to a defined level of vocalization as the nociceptive endpoint provides a reliable, highly reproducible and high through-put test for antinociception in nonrestrained mice.
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PMID:The mouse grid-shock analgesia test: pharmacological characterization of latency to vocalization threshold as an index of antinociception. 801 47

The effects of morphine and morphine withdrawal on memory performance were examined in mice by using Morris water maze task. Morphine-induced memory impairment at the doses of 5 and 10 mg/kg recovered after repeated administration. Oxotremorine, a muscarinic receptor agonist, at the dose of 0.1 mg/kg ip, and physostigmine, a cholinesterase inhibitor, at the dose of 0.1 mg/kg ip, significantly antagonized morphine (10 mg/kg sc)-induced memory impairment in mice. Furthermore, repeated naloxone (0.5 mg/kg ip) attenuated scopolamine (0.2 mg/kg ip)-induced memory impairment. By using escalating doses of morphine for 13 days, morphine-induced memory impairment was continuously maintained. When withdrawal was precipitated by naloxone (5 mg/kg ip), or administration of oxotremorine (0.1 and 0.2 mg/kg ip) or physostigmine (0.05 and 0.1 mg/kg ip), the impairment was completely reversed. These results suggest that morphine-induced memory impairment could be partially due to the inhibition of the central cholinergic activity.
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PMID:Reversal of morphine-induced memory impairment in mice by withdrawal in Morris water maze: possible involvement of cholinergic system. 1132 6

A circular and a longitudinal muscle strip were prepared from adjacent parts of a guinea-pig ileum and a direct pharmacological comparison made under identical conditions. The longitudinal preparation was sensitive to acetylcholine, methacholine, carbachol, 5-hydroxytryptamine, histamine and nicotine, while the circular preparation was insensitive to 5-hydroxytryptamine, histamine and nicotine, and responded to the choline esters only in high concentrations. Incubation of the preparations with the anticholinesterase, mipafox (NN-diisopropylphosphodiamidic fluoride), sensitized both preparations to the action of acetylcholine; potentiation of the contraction of the longitudinal muscle was 16-times; that of the circular one 4,000-times. The longitudinal muscle was more sensitive than the circular muscle to acetylcholine whether both were treated with mipafox or not. Bradykinin and substance P both stimulated the longitudinal but not the circular muscle, an effect not modified after mipafox. Hyoscine antagonized the responses of the circular muscle strip, treated with mipafox, to acetylcholine and to histamine, but on the longitudinal muscle strip the response to histamine was not affected, the response to acetylcholine being competitively antagonized. Morphine, in the same concentrations on both circular and longitudinal muscle strips, antagonized the stimulant actions of nicotine and to a lesser extent of 5-hydroxytryptamine, but the responses to histamine on the longitudinal muscle strip were not antagonized by morphine which was in contrast to its action on the circular muscle strip. These observations showed that the main differences in the responses of the circular and longitudinal muscle of the guinea-pig ileum to drugs were in the intrinsic properties of the smooth muscle cells. In addition cholinesterase may protect the circular muscle cells. Finally the circular muscle strip preparation proved to be a useful tool to study the action of drugs on the nervous plexuses of the ileum of the guinea-pig.
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PMID:SOME PHARMACOLOGICAL PROPERTIES OF THE CIRCULAR AND LONGITUDINAL MUSCLE STRIPS FROM THE GUINEA-PIG ISOLATED ILEUM. 1411 Jul 54

We studied the effect of 17 commonly used drugs, including prescription and over-the-counter medications, on the activity of serum pseudocholinesterase (PCE) in vitro. Normal pooled human serum was incubated for 120 minutes at 37 degrees C with therapeutic serum concentrations of prescription and over-the-counter drugs, and the postincubation PCE activity was measured. Morphine, quinidine, and thioridazine depressed PCE activity by more than 5% while no or negligible effect was noted following incubation with acetaminophen, chlordiazepoxide, chlorpromazine, desipramine, doxepin, imipramine, methamphetamine, nortriptyline, phenobarbital, phenytoin, procainamide, salicylic acid, theophylline, and valproic acid. Depression of PCE activity can prolong the half-life of coadministered agents with metabolism mediated by PCE.
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PMID:Studies of the inhibition of serum pseudocholinesterase activity in vitro by commonly used drugs. 1604 Feb 93

The influence of systemic administration of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference (CPP) was examined in rats. Additionally, this study aimed to compare the effects of donepezil, which selectively inhibits acetylcholinesterase, and rivastigmine, which inhibits both acetylcholinesterase and butyrylcholinesterase on morphine reward. Morphine-induced CPP (unbiased method) was induced by four injections of morphine (5 mg/kg, i.p.). Donepezil (0.5, 1, and 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5, and 1 mg/kg, i.p.) were given 20 min before morphine during conditioning phase and 20 min before the expression or reinstatement of morphine-induced CPP. Our results indicated that both inhibitors of cholinesterase attenuated the acquisition and expression of morphine CPP. The results were more significant after rivastigmine due to a broader inhibitory spectrum of this drug. Moreover, donepezil (1 mg/kg) and rivastigmine (0.5 mg/kg) attenuated the morphine CPP reinstated by priming injection of 5mg/kg morphine. These properties of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist but not scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. All effects of cholinesterase inhibitors were observed at the doses that had no effects on locomotor activity of animals. Our results suggest beneficial role of cholinesterase inhibitors in reduction of morphine reward and morphine-induced seeking behavior. Finally, we found that the efficacy of cholinesterase inhibitors in attenuating reinstatement of morphine CPP provoked by priming injection may be due to stimulation of nicotinic acetylcholine receptors.
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PMID:Influence of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference in rats. 2475 8

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