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)

Escape from acetylcholine-induced dilatation of gastric submucosal arterioles was studied using in vivo microscopy in rats. Acetylcholine, physostigmine and atropine were applied topically to the submucosa. Experiments were videotaped and diameter changes of the submucosal arterioles were measured with an image splitting technique on playback of the videotapes. Acetylcholine, 10(-6) M and 10(-5) M, caused prompt dilatation of arterioles in a dose-dependent manner, and the dilatation was rapidly followed by escape (return of vessel diameter toward basal diameter in spite of the continued presence of acetylcholine). The escape from acetylcholine-induced dilatation was prevented by physostigmine in a dose-dependent manner, 10(-2) M completely inhibiting the escape. Physostigmine, by itself, 10(-4) M to 10(-2) M, dilated arterioles dose-dependently, and this dilatation was inhibited by atropine. These results indicate that escape of gastric submucosal arterioles from acetylcholine-induced dilatation is mediated by endogenous cholinesterase (catabolism of acetylcholine by endogenous cholinesterase), and basal arteriolar diameter may be determined, in part, by endogenous acetylcholine, this effect being modulated by endogenous cholinesterase.
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PMID:Escape of gastric submucosal arterioles from acetylcholine-induced dilatation. 382 94

Ocular myasthenia is a special form of general myasthenia gravis characterized by unilateral or bilateral ptosis and eye muscle pareses of distinct variability, depending on the time of day and the state of fatigue of the patient. Most important for diagnosis is the Tensilon test, which can, however, produce negative results. In such cases a combination of the Tensilon test with electromyography is indispensable. In ocular myasthenia there is not always an increase in the antibody titer against acetylcholine receptors in the blood. The treatment of ocular myasthenia is based on the application of cholinesterase inhibitors. The drug of choice is Mestinon; however, the reaction of the eye muscles to this drug is often unsatisfactory. Local application of cholinesterase inhibitors in the form of Eserine, Prostigmin etc. is an additional important therapy. Also in ocular myasthenia the modern treatment with Cortisone (alternate-day therapy with 100 mg Prednisone every second day) has proved very useful. Another possible method of interfering with the immunological systems of myasthenia is immunosuppression with Azathioprin or Cyclophosphamide. The pathognomonic significance of the thymus in the autoimmune process of myasthenia gravis is demonstrated by the good results obtained by thymectomy, which can also be performed successfully in ocular myasthenia, not only in young patients in whom the condition is severe, but also in older patients in whom it is chronic. Often, the therapeutic measures mentioned have to be tested one after another or in combination in order to achieve an optimal therapeutic effect.
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PMID:[Ocular myasthenia]. 399 98

The choline uptake system has been characterized in the albino rat iris. The isolated iris of the rat accumulates choline (Ch) by a high affinity (Km = 3.23 microM) and a low affinity (Km = 68.4 microM) process. The uptake of 1 microM Ch at 37 degrees C was inhibited in a dose-dependent manner by hemicholinium (IC50 is 70 microM) and by ouabain (IC50 is 1 mM). The high affinity uptake was temperature and sodium-dependent. At 0 degrees C uptake of Ch was reduced by over 85% and it was not sensitive to hemicholinium. This suggests that choline is taken up by a high affinity active transport into the cholinergic terminals of the iris. The uptake of 1 microM Ch at 37 degrees C was inhibited by 1 mM scopolamine and was reduced in a dose-dependent manner by the irreversible anticholinesterase diisopropylfluorophosphate (DFP). Physostigmine, an anti-cholinesterase lacking agonistic action, decreased the uptake of Ch to 73% of control at 1 mM. The rat iris is a much more homogeneous and readily accessible tissue than the CNS, therefore, it offers several advantages in pharmacological studies of drug action on a selective population of cholinergic terminals.
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PMID:Acute effects of cholinesterase inhibitors on uptake of choline in the rat iris. 400 Apr 6

Physostigmine, a centrally-acting cholinesterase inhibitor, has been shown to have potential as a treatment for primary degenerative dementia. In an experiment to test its effects, i.v. physostigmine caused the onset of unifocal premature contractions and runs of bigeminy in an 85-year-old man.
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PMID:Dose-related physostigmine-induced ventricular arrhythmia: case report. 404 37

1. Synaptic potentials were recorded with intracellular electrodes from cells in the inferior mesenteric ganglion of the guinea-pig.2. Half-widths of the synaptic potentials recorded fell into two groups: type L cells had long synaptic potentials (11.6-15.2 msec) and low thresholds (14.6 mV mean), type S cells had short synaptic potentials (6.1-9.3 msec) and high thresholds (29.9 mV mean).3. Physostigmine (1.2 x 10(-6)M) caused a significant increase in the half-width of both types of synaptic potential.4. Physostigmine caused a significant increase in the half-width of spontaneous synaptic potentials and an increase in their amplitude.5. Repetitive preganglionic stimulation, in the presence of physostigmine, led to a marked and prolonged depolarization in all cells. In most cells repetitive spontaneous firing of action potentials was then observed. This effect was blocked by atropine (1.4 x 10(-7)M).6. The effect of atropine on the half-width in a physostigmine-treated cell was inconsistent: although synaptic potentials in some cells were slightly shortened their half-widths were always greater than the control.7. It is concluded that cholinesterase plays a role in limiting the time course of the synaptic potential, by limiting the duration of action of acetylcholine.
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PMID:The effects of physostigmine on synaptic transmission in the inferior mesenteric ganglion of guinea-pigs. 444 20

1. Acetylcholine (ACh), other cholinomimetics, cholinesterase inhibitors and cholinergic antagonists were administered iontophoretically to medial geniculate (MG) neurones and their effects on chemically or neurally evoked responses recorded extracellularly.2. Acetylcholine had excitant actions on 45% of the neurones tested. Most of these were of a slow time course. Desensitization to the excitant effects was frequently observed.3. Acetylcholine excited 91% of neurones activated antidromically by stimulation of the auditory cortex, 71% of neurones activated synaptically from the auditory cortex, 74% of neurones activated from the inferior colliculus and 100% of geniculo-cortical relay neurones.4. Acetylcholine had depressant effects, which were generally of a rapid time course, on 29% of MG neurones. No desensitization to the depressant effects was observed.5. On 4% of neurones, ACh had both excitant and depressant effects. Such "dual" effects were manifested either as an initial excitation followed by a depression, or as a depression followed by an excitation.6. Eserine, neostigmine and edrophonium potentiated both excitant and depressant actions of ACh on many cells. Neostigmine and edrophonium occasionally antagonized the effects of ACh.7. Atropine, hyoscine, dihydro-beta-erythroidine, hexamethonium and (+)-tubocurarine antagonized both excitant and depressant effects of ACh. The muscarinic blocking agents were usually more effective than the nicotinic agents.8. Carbamylcholine, acetyl-beta-methylcholine, nicotine, butyrylcholine, arecoline and pilocarpine had excitant, depressant or no effects on MG neurones. Generally, carbamylcholine was more potent than acetyl-beta-methylcholine and ACh, which were more potent than nicotine. Butyrylcholine, arecoline and pilocarpine were even less potent, often having no effect.9. The cholinomimetics generally had similar effects to those of ACh on the same neurones, but sometimes were quite different. Carbamylcholine, acetyl-beta-methylcholine and nicotine antagonized the effects of ACh on some neurones.10. The results suggest that cholinoceptive receptors on MG neurones are not homogeneous. Although there are possibly some purely muscarinic and purely nicotinic receptors, the majority appear to be of intermediate muscarinic-nicotinic type. These mediate either excitation or inhibition.
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PMID:Properties of cholinoceptive neurones in the medial geniculate nucleus. 541 82

1. Cortical slices from rat brain were incubated in media containing the irreversible cholinesterase inhibitor soman and a high KCl concentration, and the release and synthesis of acetylcholine (ACh) were determined.2. Atropine enhanced the release and synthesis of ACh.3. Tetrodotoxin, a substance which blocks nervous conduction, did not influence the release and synthesis of ACh, in the absence or in the presence of atropine. Therefore the nerve endings are probably the site at which atropine acts when stimulating the release and synthesis of ACh.4. Pretreatment of the slices with botulinum type A toxin partially blocked the release and synthesis of ACh and reduced the extra amounts of ACh released and synthesized under the influence of atropine.5. Lowering the calcium or raising the magnesium concentration in the incubation medium reduced the release and synthesis of ACh and their enhancement by atropine.6. Physostigmine decreased the total extractable ACh content of the slices during incubation in a 25 mM KCl containing medium. This decrease was nearly prevented when the release and synthesis of ACh were inhibited by omission of the calcium ions from the medium, but was enhanced by atropine.7. The observations made with pretreatment by botulinum type A toxin, with changes in the calcium and magnesium concentration as well as with physostigmine, all support the theory that it is primarily the release of ACh which is enhanced by atropine and that its stimulating action on the synthesis results from the increased release.
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PMID:Stimulation by atropine of acetylcholine release and synthesis in cortical slices from rat brain. 549 92

Physostigmine (PHY; eserine) prolongs the action potentials in the Retzius cells within leech ganglia to about 800 ms. The effect was reversible and occurred at concentrations of 1-10 mM which are several orders of magnitude greater than those required to inhibit cholinesterase. The prolonged action potentials showed an early, spike-like depolarization followed by a plateau. The initial depolarization exhibited a strong dependence on external Na+ while the amplitude of the plateau had somewhat less Na+ dependence: 52 and 24 mV/decade, respectively. The duration of the plateau was increased by elevating Na+ and decreased by elevating Ca2+. Increasing the action potential frequency, by intracellular stimulation, decreased both the duration and amplitude of the plateau. Neostigmine, di-isopropylphosphofluoridate, and acetylcholine did not prolong RZ action potentials. Thus, the membrane effects of physostigmine appear to be independent of any inhibition of cholinesterase or accumulation of acetylcholine.
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PMID:Action potential prolongation: an effect of physostigmine (eserine) upon Retzius cells in the leech C.N.S. 614 81

Clonidine, an alpha-2 adrenergic agonist can inhibit the release of acetylcholine from central and peripheral cholinergic neurons. This study was designed to examine the ability of clonidine to protect animals from the toxic manifestations of cholinesterase poisoning. Physostigmine, a central and peripheral cholinesterase inhibitor produced tremors, and at high doses death, by respiratory paralysis. Mice were injected with physostigmine at a dose (0.75 mg/kg) which evoked tremors in 100% and death in 90% of the animals. Clonidine pretreatment (0.3 mg/kg) increased the onset latency to tremor from 5 to 20 min, increased the onset latency to death from 12 to 24 min and increased the percentage of survivors to 50%. Yohimbine (1 mg/kg) reversed these protective effects of clonidine. The physostigmine-induced accumulation of forebrain and hindbrain acetylcholine also was reduced by 50% in both brain regions in clonidine-pretreated mice. Neostigmine, a selective peripheral cholinesterase inhibitor, induced respiratory paralysis which was not affected by clonidine pretreatment. These findings indicate that central cholinergic neurons involved in the regulation of respiration and fine motor control, but not peripheral motor neurons, are inhibited by clonidine acting on alpha receptors.
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PMID:Mechanism of the clonidine-induced protection against acetylcholinesterase inhibitor toxicity. 628 26

Cholinesterase inhibitors are known to potentiate the effects of acetylcholine (ACh) and vagal stimulation on the myocardium. The studies presented here demonstrate that cholinesterase inhibitors (ChEI) also have activity in isolated atria in the absence of extrinsic cholinergic stimulation and that, depending on the ChEI, either indirect stimulation or direct blockade of cardiac muscarinic receptors can occur. Muscarinic agonists inhibit cyclic AMP formation in atria and the ChEIs physostigmine, neostigmine and echothiophate likewise produce a marked attenuation of isoproterenol-stimulated cyclic AMP accumulation The effect of physostigmine appears to result from muscarinic receptor activation by endogenous ACh as it is blocked by atropine. In contrast, the ChEI ambenonium does not stimulate but instead blocks muscarinic receptors coupled to cyclic AMP accumulation. Radioligand binding studies provide direct evidence that both ambenonium and demecarium are relatively potent muscarinic receptor antagonists, whereas physostigmine and other ChEI have little direct receptor activity. Physostigmine and ambenonium also have different effects on heart rate in vivo, the former potentiating and the latter apparently blocking vagal tone. The inhibition of cyclic AMP formation produced by physostigmine can be used as a measure of the concentration of endogenous ACh available at muscarinic receptor sites. Physostigmine blocks cyclic AMP formation in atria incubated in the absence of calcium or in the presence of tetrodotoxin, suggesting that endogenous ACh is spontaneously released in the absence of neuronal activity or depolarization-secretion coupling.
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PMID:Activation and blockade of cardiac muscarinic receptors by endogenous acetylcholine and cholinesterase inhibitors. 628 18


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