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)

Several identified neurons of the Aplysia buccal ganglia respond to choline. Iontophoretic applications of either choline or acetylcholine (ACh) to voltage-clamped inhibitory follower neurons produce similar currents. Peak amplitudes of choline responses were 10-100% of ACh responses on the same cell. Choline currents were curare blockable and reversed at -69 +/- 2 mV, within 1 mV of postsynaptic current (IPSC) reversal. Application of 1 mM choline to the bath produces more prolonged effects than an initial conductance change. Choline depressed IPSC amplitude by 42 +/- 5% and prolonged IPSC decay time constant by 25 +/- 7%. The slowing was reversible but the depression was not. Use of choline as a Na substitute may therefore involve unexpected partial agonist action; even where conductance changes are transient or inapparent, choline may alter synaptic responses. Bath choline had variable effects on cholinergic self-inhibitory synapses, blocking in six trials but not in three others. Voltage clamping cells BL and BR7, in which monosynaptic cholinergic PSPs are diphasic, reveals underlying early inward and late outward currents. Choline activates only the late outward current component. Correspondingly, bath choline blocks only the late outward component, as does eserine and ACh. This block is not seen with neostigmine, and so is unlikely to be related to cholinesterase inhibition. The early inward current component, revealed by block of the late component by choline or ACh, decays exponentially. Decay time constant is exponentially dependent on membrane potential over the range -20 to -100 mV, with 63-mV depolarization speeding decay e-fold. Eserine prolongs decay and steepens voltage dependence. The late outward component decays with voltage-independent time constant of 48 +/- 5 ms. Both the time integral of synaptic conductance and the ratio of synaptic charge transfer to peak synaptic current of the early inward component of the cell 7 response are reduced by depolarization. Voltage-dependent duration thus combines with reduced driving force in diminishing the excitatory effect of this component at depolarized levels, allowing the inhibitory component to predominate. In this diphasic synapse, voltage dependence of the time course of one component thus serves an easily identified function.
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PMID:Choline acts as agonist and blocker for Aplysia cholinergic synapses. 631 20

Thymoxamine, 6-acetoxythymol-2-dimethylaminoethyl ether, is a competitive alpha-adrenoceptor blocking agent used as a vasodilator in the treatment of peripheral vascular disorders. The plasma half-life of the drug in vivo is very short. In vitro experiments showed that thymoxamine had a half-life in human plasma of about only 1 min. By using the compound as a substrate in increasing concentrations from 5-320 microgram/ml in the presence of a fixed, low concentration of plasma (0.1% v/v) at pH 7.4 and 37 degrees a hyperbolic correlation was found between the concentration of thymoxamine and the initial rate of formation of the involved reaction product, which was determined by HPLC. A linearized Michaelis-Menten plot indicated an enzymatic biotransformation. A Km-value of about 0.115 mumol ml-1 and a Vm-value of about 0.0037 mumol ml-1 min.-1 were found. Physostigmine, neostigmine and cinchocaine inhibited the biotransformation competitively. This indicated that plasma cholinesterase was the enzyme responsible. The metabolite was identified as desacetylthymoxamine by HPLC, spectrophotometry and direct inlet mass spectrometry.
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PMID:Plasma induced biotransformation of thymoxamine and its kinetics. 644 31

The space adaptation syndrome is one of the more vexing problems confronted by our nation's astronauts during their journeys. This syndrome may be a variant of motion sickness, although this possibility has been questioned. Physostigmine, a centrally active cholinesterase inhibitor which increases brain acetylcholine, was found to cause a motion sickness-like syndrome--in psychiatric patients and normals--including nausea, emesis, malaise, dysphoria, increases in serum ACTH, beta-endorphin, cortisol, and prolactin, Neostigmine, a non-centrally acting cholinesterase inhibitor, and saline placebo caused no such effects. The above effects closely parallel those of motion sickness. Thus, the effects of physostigmine may be a convenient model for screening for treatments for motion sickness or space adaptation syndrome, or for predicting who will develop these syndromes.
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PMID:A cholinomimetic model of motion sickness and space adaptation syndrome. 648 3

This paper reports the use of an RF capacitance field transducer and spectral analysis to examine the effects of the cholinesterase inhibitor physostigmine on the behavior of unrestrained rats. The technique is shown to permit simultaneous quantification of changes in a variety of motor behaviors. Physostigmine induced a dose-related increase in high-frequency movements and reduced low-frequency movements, but had no effect upon habituation of five to ten Hz movements which occurred with continuous exposure to the testing apparatus.
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PMID:Quantitative analysis of physostigmine-induced changes in behavior. 650 53

The present report concerns the effects of cholinergic agonists on the isometric tension of "in vitro" preparations of the esophagus and distal part of the small intestine of the lizard Liolaemus gravenhorsti. Acetylcholine (Ach) and carbachol elicited a dose-related increase of isometric tension in the esophagus, whereas the small intestine was slowly relaxed by these drugs. Eserine induced a synergistic action on the cholinergic responses of both organs, and atropine completely antagonized the respective effects. The esophagus and the intestine showed different thresholds for the cholinergic evoked responses, the former being about 30 times more sensitive than the intestine. Assessment of cholinesterase activity revealed that Ach is hydrolyzed at a significant lesser speed in the intestine than in the esophagus. The results do not provide information about the nature of the chemical mediator causing the inhibitory effect observed in the intestine. The eventual role of an adrenergic mechanism mediated by muscarinic receptors is under study in our laboratory.
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PMID:Inhibitory effect of acetylcholine on muscular tonus of the small intestine of a lizard. 673 99

1 Physostigmine (0.1-1 mM) induced dose-dependent negative and neostigmine (0.1-1 mM) positive inotropic effects on driven guinea-pig isolated atria. Physostigmine decreased and neostigmine increased cardiac frequency of spontaneously beating atria. 2 The depression of amplitude of contraction by physostigmine cannot be attributed to its inhibitory effect on tissue cholinesterase. The negative inotropic action of physostigmine is not influenced by preincubation with atropine. 3 The positive inotropic effect of neostigmine is not caused by a nicotine-like action of the drug. Neostigmine (1 mM) counteracts the negative inotropic effect of acetylcholine. The possible mechanisms of action are discussed.
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PMID:The inotropic and chronotropic effects of physostigmine and neostigmine on guinea-pig isolated atria. 711 61

1. Presynaptic cholinergic-adrenergic interactions were studied on isolated perfused rabbit atria with the extrinsic right vagus and sympathetic innervation intact. The transmitter stores were labelled with 14C-choline and 3H-noradrenaline. The radioactive compounds were separated on columns and determined by scintillation spectrometry. The stimulation-evoked overflow of both transmitters was calcium-dependent and abolished by tetrodotoxin. 2. Methacholine caused a concentration-dependent decrease of atrial tension development and 3H-noradrenaline overflow evoked by 3 Hz sympathetic stimulation. Vagus nerve stimulation (1-20 Hz), although nearly abolishing tension development at 20 Hz, decreased evoked 3H-noradrenaline overflow by not more than 18%. 3. Physostigmine decreased atrial cholinesterase activity by 80% and increased the fraction of stimulation-evoked unhydrolyzed 14C-acetylcholine in the persufates from 58 to 86%. However, the inhibition by vagus stimulation (1-10 Hz) of evoked 3H-noradrenaline overflow was smaller than in the absence of the drug. This was closely related to a decrease in acetylcholine overflow. Yet for a give fractional rate of acetylcholine release the muscarinic inhibition of noradrenaline overflow still did not exceed that observed in the absence of physostigmine. 4. It is concluded that the vagally induced control of noradrenaline release occurs at discrete sites rather than in a diffuse pattern at multiple terminal axon sites as is the case after exogenous muscarinic agonists.
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PMID:The effect of physostigmine on the vagally induced muscarinic inhibition of noradrenaline release from the isolated perfused rabbit atria. 712 14

It has been shown that some reversible cholinesterase (ChE) inhibitors as physostigmine and pyridostigmine are prophylactically effective in organophosphate poisoning. The inhibition and protection of ChE against Soman poisoning with the above mentioned drugs was investigated in mice. (1) Physostigmine and pyridostigmine significantly inhibited the ChE in whole blood in vivo and their inhibitory potencies with equitoxic doses were approximately equal (1/5LD50 about 30%; 1/2 LD50 about 45% respectively). Physostigmine also significantly inhibited brain ChE and its potency was slightly weaker than that in blood; but pyridostigmine only slightly inhibited brain ChE (17%) with large dose (1/2 LD50). The extent of inhibition was in parallel with the dosage of the drugs used. (2) Physostigmine had definite protection in the blood and brain ChE against Soman poisoning. The extent of protection was in parallel with the dosage used. The protection of blood ChE by pyridostigmine was weaker than that by physostigmine. There was no protection of brain ChE by pyridostigmine. (3) The inhibitory potency of equitoxic doses of physostigmine and pyridostigmine in the ChE of diaphragm muscle was equal too (1/2 LD50 about 45%), and the protective effect of physostigmine was still greater than that of pyridostigmine in Soman poisoning. (4) The time course of blood ChE inhibition by physostigmine in vivo was of short duration. While 30 minutes after administration of physostigmine, the ChE activity gradually recovered and it returned to normal level after 4 hours. The blood ChE inhibition by pyridostigmine reached a peak level after 2 hours, and the ChE activity slowly increased after 4 hours, but there was 30% of ChE activity still inhibited after 8 hours. Physostigmine and pyridostigmine, the reversible ChE inhibitors with carbamate structure, have definite ChE protection against Soman poisoning. The prophylactic efficacy was obviously correlated with their ChE protective potency. Evaluating physostigmine and pyridostigmine based on their efficacy, toxicity, adverse effects, duration, availability and stability, we recommend that pyridostigmine is the drug of choice in the prophylaxis against nerve gas poisoning.
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PMID:The inhibition and protection of cholinesterase by physostigmine and pyridostigmine against Soman poisoning in vivo. 718 86

Physostigmine and neostigmine were compared for their effects on shuttle-box avoidance acquisition and retention. Physostigmine impaired acquisition at doses lower than neostigmine. Avoidance performance 1, 7, or 14 days after acquisition was impaired by the administration of 0.4 mg/kg physostigmine or an equimolar dose of neostigmine. The effects of lower doses of physostigmine, but not of neostigmine, were dependent upon the time of original training relative to drug administration and retesting. The results suggest that the peripheral effects of higher doses of cholinesterase inhibitors impair avoidance performance. The effects of lower doses of physostigmine on acquisition and the time-dependent effects on subsequent performance are probably due to the central actions of this drug.
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PMID:Time-dependent changes in the effects of cholinesterase inhibitors on shuttle-box avoidance. 740 3

Survival under hypoxia (5% O2; 95% N2) was tested in mice 1 day to 50-weeks-old. Survival Rate (ratio of number of animals that survived 30 min under 5% O2 to total number of animals exposed) and the time from onset of exposure until the last gasp (Survival Time) were maximum in newborn animals and decreased as a function of age. Survival Rate and Survival Time were strongly influenced by drugs affecting cholinergic transmission. Atropine decreased the high survival under hypoxia of 1-week-old mice in a dose-related manner. Physostigmine increased survival under hypoxia in mice 3 to 50-weeks-old. This effect was not related to a peripheral action of the drug since it was not mimicked by neostigmine, a cholinesterase inhibitor without central actions. Moreover, peripheral cholinergic blockade with glycopyrrolate, a quaternary cholinergic blocker, did not prevent the protective effect of physostigmine. Since atropine impairs the ability of very young mice to survive hypoxia and physostigmine improves survival at later ages, it is concluded that a central cholinergic mechanism, possibly related to blood flow regulation, plays a significant role in the acute adaptation to hypoxia.
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PMID:Survival under hypoxia. Age dependence and effect of cholinergic drugs. 742 86


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