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)

Using tension-recording methods, we compared the effects of acetylcholine (Ach) and carbachol on the bovine iris sphincter. The isolated muscle strips were mounted in a 0.2 ml organ bath, through which Krebs solution at 36 degrees C flowed continuously. There was a ten-thousandfold difference in potency between carbachol and Ach in this tissue. Neostigmine or eserine, acetylcholinesterase (AchE) inhibitors, produced a larger contraction of the muscle than did Ach. Ach-induced contractions were potentiated by low doses of anti-AchEs and were inhibited by atropine. This in vitro study suggests that Ach and/or endogenous chemical agents may be spontaneously released from tissues and that AchE activities in this tissue strongly inhibit or mask the Ach action, probably in order to protect the nerve terminals from released Ach.
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PMID:Possible mechanisms related to contraction of the bovine iris sphincter in the presence of acetylcholine and carbachol. 325 17

1. The effects of neostigmine and physostigmine, reversible carbamate acetylcholinesterase (AChE)-inhibitors, on nicotinic acetylcholine-induced inward currents (IACh) were investigated in enzymatically isolated single sympathetic ganglion cells from the bullfrog. The 'concentration clamp' technique which combines intracellular perfusion with a rapid external solution change under single electrode voltage-clamp conditions was used. 2. Pretreatment with neostigmine and physostigmine did not enhance IACh at any concentrations, suggesting that AChE activity had already disappeared during the enzymatic treatment of the preparation. 3. Both neostigmine and physostigmine inhibited IACh in a dose-dependent manner with IC50 values of 7.0 x 10(-4) M and 1.1 x 10(-4) M, respectively. The blockade by neostigmine was competitive, while that by physostigmine was non-competitive. 4. The inhibition of IACh by neostigmine and physostigmine showed no apparent voltage dependency. 5. Neostigmine did not cause obvious changes of the kinetics of IACh. However, physostigmine reduced both the fast and slow time constants of inactivation of IACh, thus facilitating the rate of inactivation without affecting the activation kinetics of IACh. 6. These results suggest that neostigmine and physostigmine have different direct actions on the ACh receptor-ionophore complex. Neostigmine may act on the ACh-receptor (the binding site of ACh) while physostigmine may interact with the ACh-gated cation channels.
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PMID:Effects of neostigmine and physostigmine on the acetylcholine receptor-ionophore complex in frog isolated sympathetic neurones. 339 92

Neostigmine (0.5-2 microM) caused fade of tetanic contractions (Wedensky inhibition) evoked by repetitive nerve stimulation. The mechanism underlying this action was studied in intact and cut isolated phrenic nerve-diaphragm preparations of mice. The fade was brought about by failure to elicit muscle action potentials. During fade, the muscle was unable to conduct directly evoked action potentials across the central endplate zone. Recovery of excitability occurred in 5 s with continued stimulation. In the presence of neostigmine, the resting membrane potential at endplate areas during repetitive stimulation decreased from -80 mV to less than -50 mV within the first 10 pulses at 75-200 Hz and thereafter recovered gradually to about -60 mV in the following 5 s during continuous stimulation. The quantal content of endplate potentials evoked by single stimulation was not reduced by neostigmine whereas that evoked by high frequency stimuli (75 Hz) was reduced to about 1/3 in 10 pulses. It is concluded that the fade of tetanic contraction caused by inhibition of acetylcholinesterase is induced by the inactivation of sodium channels in the area surrounding the endplates and that the sustained fade is due to a decrease of transmitter release. Both effects are the result of acetylcholine accumulation.
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PMID:Mechanisms of the inhibition by neostigmine of tetanic contraction in the mouse diaphragm. 370 8

To investigate the ontogenesis of potential cholinergic influences on growth hormone secretion we administered the cholinesterase inhibitor neostigimine, (120 micrograms/kg) to fetal sheep (n = 16) between 77 and 143 days of gestation and to infant lambs (n = 5). Neostigmine administration was associated with a marked rise in fetal growth hormone concentrations. The integrated release of growth hormone in the hour following fetal neostigmine administration was 2880 +/- 425 ng.min/ml compared to -618 +/- 206 ng . min/ml (P less than 0.001) following saline administration (n = 19). There was no relationship between gestational age and the response to neostigmine. In the infant lamb, neostigmine was associated with a lesser (P less than 0.001) but significant (P less than 0.02) growth hormone response. The integrated release was 704 +/- 410 ng . min/ml (n = 5) compared to -44 +/- 40 ng . min/ml following saline (n = 11). The fetal response to neostigmine was abolished by the administration of atropine (200 micrograms/kg bolus followed by 400 micrograms/kg per h infusion) 5 min prior to neostigmine (n = 4). This demonstrates that the effect of neostigmine was mediated by muscarinic receptors. Atropine itself had no effect on fetal growth hormone release (n = 6). In vitro binding studies with the muscarinic ligand, 1-quinuclidinyl [phenyl-4 (n) -3H] benzilate) were performed on homogenates of fetal (n = 3) and adult (n = 3) pituitaries. Scatchard analysis demonstrated both a high affinity and low affinity binding site. The concentration per mg. of original tissue of each of these binding sites was higher (P less than 0.05) in fetal than adult homogenates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Muscarinic influences on growth hormone secretion in the fetal and neonatal sheep: pharmacological studies and in vitro binding studies. 407 57

1. Studies were made on the effects of iontophoretically and intravenously administered cholinergic antagonists on the synaptic responses of medial geniculate (MG) neurones evoked by stimulation of the auditory cortex, inferior colliculus and mesencephalic reticular formation.2. Atropine specifically blocked a proportion of the excitatory responses evoked by stimulating the auditory cortex, inferior colliculus and reticular formation, although it was without effect on some of them.3. Neostigmine and eserine facilitated some excitatory synaptic responses evoked by inferior collicular stimulation.4. It is suggested that the feline MG nucleus receives excitatory cholinergic, as well as non-cholinergic, pathways from the auditory cortex, inferior colliculus and lower brain stem. The cholinergic pathways from the auditory cortex may be either corticofugal fibres or recurrent axon collaterals of afferent projections from the MG nucleus to the cortex. Those from the lower brain stem are possibly the cholinesterase-containing fibres described by Shute & Lewis (1967).
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PMID:Studies on cholinergic transmission in the medial geniculate nucleus. 431 29

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

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

1 The effects of neostigmine on noradrenergic transmission have been studied in the field stimulated, isolated anococcygeus muscle of the rat. 2 In those muscles where the excitatory response to field stimulation was not completely inhibited by guanethidine (5 X 10(-6) to 10(-5) M) or phentolamine (10(-6) M), atropine (5 X 10(-8) M) gave no further inhibition of the response. 3 The shape of the response to field stimulation was altered in a dose-dependent manner by neostigmine (5 X 10(-7) to 5 X 10(-6) M), such that a 'shoulder' appeared during the relaxation phase. The 'shoulder', present at all stimulation frequencies tested between 3 and 40 Hz, was abolished by atropine (5 X 10(-8) M) and unaffected by tubocurarine (10(-6) M). 4 Neostigmine (2.5 X 10(-6) M), whether alone or in the presence of atropine (5 X 10(-8) M), had no effect on the uptake or stimulation-induced release of [3H]-noradrenaline. 5 Using electron microscopy, small Schwann/axon bundles close to smooth muscle cells rarely showed cholinesterase staining, whereas larger bundles at the outer serosal aspects of the muscle exhibited dense staining. 6 It is concluded that the observed effects of neostigmine are not due to a presynaptic effect on noradrenergic transmission.
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PMID:Neostigmine augments responses of the rat anococcygeus muscle to field stimulation. 629 49

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


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