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)

The responsiveness of Aplysia acetylcholine receptors (AChR) was studied using a polyene antibiotic, filipin, which specifically complexes cholesterol, and another compound, chlorpromazine (CPZ), which inserts at the proteolipidic interface. Both substances enhanced the evoked postsynaptic responses or responses to iontophoretic application of carbachol only on the H-type receptor (opening a Cl-permeability), whereas at the same concentrations filipin was without effect on the D-type receptor (opening a cationic permeability) while CPZ depressed the D-type response. The facilitation observed specifically for the H-type receptor was similar to that previously described after acetylcholinesterase (AChE) inhibition or when low concentrations of detergents were applied to this preparation. No additive effect was obtained after the addition of chlorpromazine following a maximal potentiation obtained with an anticholinesterase agent. Since at Aplysia central neurons, AChE is a membranal protein, we propose that the facilitation of H-type responses is attributable to the removal of a modulatory action of AChE on AChR. Filipin or chlorpromazine might disrupt the interaction between AChR and AChE.
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PMID:Modulation of an acetylcholine receptor responsiveness by filipin and chlorpromazine studied in neurons of Aplysia californica. 359 17

1. Miniature postsynaptic currents were analyzed at an inhibitory cholinergic neuroneuronal synapse in the buccal ganglion of Aplysia. Under double voltage-clamp, it was possible to induce postsynaptic currents by long-duration depolarizations of the presynaptic neuron and to analyze these as the linear summation of individual miniature postsynaptic currents (MPSCs). The amplitude of these miniature currents (imin) was calculated from the ratio of the variance of the noise (E2) to the mean of the postsynaptic current (Im), according to Campbell's theorem, with imin = 2E2/Im. Their decay time (tau min) was obtained from the cutoff frequencies of the power spectra obtained from the noise. 2. Neither the conductance nor the decay time of MPSCs was voltage dependent. However, imin appeared to decrease when the quantal content of the response increased. Meanwhile, tau min increased slightly with Imin. 3. Carbamylcholine was injected into the neuropile and this led to a decrease in imin and a slight increase in tau min. 4. Power spectra obtained after the application of inhibitors of acetylcholinesterase (AChE), with or without curare, suggested that acetylcholine (ACh) does not accumulate during large depolarizations. 5. The possible origin of the nonlinear relationship between the variance and the mean of the postsynaptic currents is discussed.
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PMID:Properties of miniature postsynaptic currents during depolarization-induced release at a cholinergic neuroneuronal synapse. 365 14

The effects of the carbamate anticholinesterases neostigmine and pyridostigmine on the kinetics of desensitization of responses of isolated, voltage-clamped Aplysia neurons to microperfused acetylcholine (ACh) was examined. The peak ACh-induced current was potentiated at low carbamate doses and antagonized at higher doses (greater than 10(-5) M); neostigmine was more potent than pyridostigmine in producing both effects. These effects suggest two mechanisms of action of these compounds: (a) inhibition of acetylcholinesterase at low doses, which increases the effective ACh dose, and (b) direct antagonism of the response at higher concentrations, which is associated with a slowing of both the activation and desensitization of the ACh response. These compounds may therefore have direct actions on the excitatory ACh receptor in Aplysia neurons which are similar to the effects of these drugs at the vertebrate endplate.
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PMID:Multiple interactions of anticholinesterases with Aplysia acetylcholine responses. 373 Aug 31

Fasciculin II, a potential inhibitor of acetylcholinesterase (AChE), was tested on two types of Aplysia cholinergic receptors: H type, opening Cl- channels; and D type, opening cationic channels. Evoked postsynaptic inhibitory responses and responses to ionophoretic application of acetylcholine (ACh) or carbachol onto H-type receptors were potentiated in the presence of fasciculin II at 10(-9) M, whereas the same concentration of this drug was without effect on the evoked postsynaptic excitatory responses or on the application of ACh or carbachol on D-type receptors. The observed effects of fasciculin II were identical to those obtained with other inhibitors of AChE on the same preparation. The facilitatory effect on the carbachol response in H-type cells indicates that fasciculin II, as other AChE inhibitors, does not act on H-type synapses solely by blocking the hydrolysis of ACh. We concluded that fasciculin II was a good inhibitor of acetylcholinesterase on neuronal preparations in vivo. The results are further discussed as a new element in favor of a previously proposed hypothesis of a molecular interaction between AChE and ACh H-type receptors.
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PMID:Fasciculin II, a protein inhibitor of acetylcholinesterase, tested on central synapses of Aplysia. 373 Dec 16

Carbachol was injected into a presynaptic cholinergic neuron in the buccal ganglion of Aplysia and the quantal aspects of the Cl- -dependent postsynaptic response to a prolonged stimulation were analyzed by a statistical fluctuation method. The calculated amplitude of the miniature postsynaptic current was increased with respect to control. Statistical fluctuation analysis was also used to analyze the postsynaptic response obtained during ionophoretic application of acetylcholine and carbachol. The calculated unitary channel current was found to be greater for carbachol than for acetylcholine. This increase could explain the larger miniature postsynaptic current seen after intracellular injection of carbachol into the presynaptic neuron if carbachol was released at the synapse as a false transmitter. This conclusion was supported by the observation that it was possible to restore transmission at a synapse previously blocked by presynaptic intracellular injection of acetylcholinesterase with a presynaptic injection of carbachol.
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PMID:Carbachol can be released at a cholinergic ganglionic synapse as a false transmitter. 613 41

Most of the effects of acetylcholinesterase (AChE) on synaptic transmission are considered to be related to its acetylcholine (ACh) hydrolysing properties. This is clearly apparent from changes which occur in the characteristics of the miniature endplate potential and of the endplate potential at neuromuscular junctions when AChE is inhibited1-4 and during the development of enzymatic AChE activity at maturing synapses5. However, we report here that after inhibiting AChE in a cholinergic synapse in Aplysia, we found an increase not only in postsynaptic responses to presynaptic stimulation and to ionophoretic application of ACh on postsynaptic receptors, but also to ionophoretic application of carbachol. This could not be explained by the inhibition of the ACh hydrolysing function of the enzyme, as carbachol is not hydrolysed by AChE. A possible explanation of these observations is that inhibition of the enzyme affects a property of the ACh receptor (AChR) itself.
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PMID:Possible role of acetylcholinesterase in regulation of postsynaptic receptor efficacy at a central inhibitory synapse of Aplysia. 629 31

The action of an irreversible inhibitor of acetylcholinesterase (AChE), the organophosphorus compound, ecothiopate iodide, and of a reactivator of phosphorylated AChE, contrathion, were analysed on acetylcholine (ACh) receptors and cholinergic synaptic transmission in the buccal ganglion of Aplysia. At high concentration (above 10(-4)mol X 1(-1), both compounds exerted a curare-like depression on ACh receptors which was reversible with washing. Both compounds reversibly facilitated the current response to ionophoretic application of ACh and increased the evoked postsynaptic current (PSC) as well as the miniature postsynaptic currents (MPSCs). All responses also showed an increase in decay time. These modifications, when induced by ecothiopate iodide were irreversible by washing; however they could be reversed if first washed with contrathion. Neither the organophosphate compound or the oxime did change the number of quanta released per impulse. The current response to ionophoretic application of carbachol also increased after ecothiopate iodide was added. In the limits of the method used, the conductance and opening time of postsynaptic ionic channels opened by ACh were not found to be modified by the two compounds. It was concluded that the facilitatory action of the organophosphorus inhibitors cannot be solely explained by the inhibition of ACh hydrolysis.
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PMID:Direct and indirect effects of an organophosphorus acetylcholinesterase inhibitor and of an oxime on a neuro-neuronal synapse. 630 Jul 51

The side effects of four phosphorylated cholinesterase reactivators (oximes): contrathion, TMB4, toxogonine and 1574 SEBC on membrane properties and synaptic transmission of Aplysia central neurons were investigated. Applied in the bath at 10(-3) mol X 1(-1) to 10(-2) mol X 1(-1) concentrations, all these oximes had a depressive action on cholinergic transmission exerting a curare-like effect on the postsynaptic receptors. In addition, Toxogonin and TMB4 affected the presynaptic voltage dependent sodium conductance. None of these oximes interfered with the voltage dependent potassium or calcium conductances. The oximes had a transient facilitatory action on amplitude of the response to ionophoretically applied acetylcholine (ACh) on H-type ACh receptors, but not on cells with D-type ACh receptors. The K+ dependent response to ACh injection on pleural ganglion cells was selectively blocked by 5 X 10(-6) mol X 1(-1) contrathion. All oximes at 10(-2) mol X 1(-1) to 10(-3) mol X 1(-1) similarly depressed serotonin receptors in buccal ganglion cells. All the effects of oximes were reversible by washing. It was concluded that oximes can act as 1) inhibitors of Na+ conductance, 2) antagonists for various synaptic receptors, 3) reversible inhibitors of acetylcholinesterase.
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PMID:Side effects of phosphorylated acetylcholinesterase reactivators on neuronal membrane and synaptic transmission. 630 Jul 53

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

At Aplysia H- and D-type cholinergic neuro-neuronal synapses, application of high concentrations of detergents (Triton X-100 and sodium deoxycholate) depressed synaptic transmission and the postsynaptic response to ionophoretic application of acetylcholine (ACh) or carbachol. However, when very low concentrations of detergents (of the order of 10(-9) M for sodium deoxycholate) were used, the nerve-evoked response as well as the ACh and carbachol ionophoretic responses were facilitated (by at least 200%), but only in H-type cells. This facilitation was similar to that previously observed in the same receptor type when acetylcholinesterase (AChE) was inhibited by various organophosphate or carbamate acetylcholinesterase inhibitors (AChEIs)3. Indeed, the effects of AChEI and detergents were not cumulative. We propose that on H-type synapses detergents may perturb a hypothetical molecular interaction between AChE and the acetylcholine receptor (AChR) by which AChE modulates the ability of the AChR to be activated by ACh or carbachol.
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PMID:Postsynaptic acetylcholine receptor efficacy is similarly increased by detergents and acetylcholinesterase inhibitors at an Aplysia synapse. 647 13


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