Activation and Blockade of the Nicotinic and Glutamatergic Synapses by Reversible and Irreversible Cholinesterase Inhibitors

Albuquerque, Edson X.; Aracava, Yasco; Idriss, M.; Schönenberger, Bernhard; Brossi, Arnold; Deshpande, Shripad B.

doi:10.1007/978-1-4684-5266-2_25

Cited by 20 publications

(15 citation statements)

References 35 publications

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“…The results showed that all of these agents including the OP compounds altered the kinetics of the AChR by acting as weak agonists or noncompetitive blockers. In addition, our studies disclosed that the targets of OPs and carbamates were not restricted to cholinergic synaptic elements; glutamate-activated postsynaptic receptors were similarly affected by these compounds (Idriss et aL, 1986).…”

Section: Introductionmentioning

confidence: 89%

“…In adultion, these agents, except tabun, also interacted postsynaptically at locust neuromuscular synapse (Idriss et al, 1986).…”

Section: The Effects Of (-)mentioning

confidence: 99%

“…The effects of VX on the glut~aa*e-activated single channel currents were determined from noise analysis experiments performed in the locust VX, at a holding potngtial of -47 mV, decreased channel lifetime from 1.7 to 1.2 mucc (Idriss et al, 1986).…”

Section: Preand Postsynaptic Effects Of the Anti-che Agents On The Lomentioning

confidence: 99%

“…In additinn to well known anti--XE properties of carbamates at the chonlnergic synapses which have been studied in detail by Karczmar Studies with a number of reversible and irreversible inhibitors of ChE have shown that, in addition to diruct actions on the nicotinic AChR complex , these agents interact with the preand postsynaptic components of the insect glutamatergic neuromuscular synapses (Idriss and Albuquerque, 1985b;Idriss et al, 1986;Rao et al, 1986).…”

mentioning

confidence: 99%

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Molecular Targets and Synaptic Effects of Carbamates, Organophosphates, Oximes, and Pyridiniums: Implications for Prophylaxis and Therapy of Organophosphate Toxicity

Albuquerque¹

1994

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Section: Introductionmentioning

confidence: 89%

“…In adultion, these agents, except tabun, also interacted postsynaptically at locust neuromuscular synapse (Idriss et al, 1986).…”

Section: The Effects Of (-)mentioning

confidence: 99%

Section: Preand Postsynaptic Effects Of the Anti-che Agents On The Lomentioning

confidence: 99%

mentioning

confidence: 99%

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Molecular Targets and Synaptic Effects of Carbamates, Organophosphates, Oximes, and Pyridiniums: Implications for Prophylaxis and Therapy of Organophosphate Toxicity

Albuquerque¹

1994

Self Cite

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“…Recently, we found with intracellular recording techniques that the application of soman immediately inhibited the membrane hyperpolarization mediated by the muscarinic receptors in cat bladder parasympathetic neurones (Kumamoto & Shinnick-Gallagher, 1988). It is well known that AChE inhibitors induce not only the persistence of ACh in the synaptic cleft due to AChE inhibition, but also other actions (see Karczmar, 1984, for review), including a blockade of the nicotinic ACh receptor-ion channel complex (Kuba et al, 1974;Albuquerque et al, 1987). Therefore, the acute soman-induced depression of muscarinic hyperpolarization may be due to an action independent of AChE inhibition.…”

Section: Introductionmentioning

confidence: 99%

Action of an irreversible acetylcholine esterase inhibitor, soman, on muscarinic hyperpolarization in cat bladder parasympathetic ganglia

Kumamoto

Shinnick‐Gallagher

1990

British J Pharmacology

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1 Intracellular recording techniques were used to examine the action of an irreversible acetylcholine esterase (AChE) inhibitor, soman, on the hyperpolarizations mediated through muscarinic cholinoceptors in cat bladder parasympathetic neurones. 2 Soman (0.1-10gM) depressed the amplitude and prolonged the duration of the muscarinic slow inhibitory postsynaptic potential (s-i.p.s.p.) elicited by a preganglionic tetanus (40 Hz for 1 s) in the presence of mecamylamine (20pum), phentolamine (1 pM) and caffeine (1 mM), in a dose-dependent manner. The effect of soman on the amplitude of the s-i.p.s.p. was partially reversible, while the effect on the duration was irreversible. 3 Soman hyperpolarized the membrane and decreased input resistance, but this effect could not account for soman-induced inhibition of the s-i.p.s.p. 4 Soman depressed the amplitude and prolonged the duration of a muscarinic hyperpolarization induced by pressure application of acetylcholine (ACh) in the presence of mecamylamine, phentolamine and caffeine. The time course of this effect paralleled that on the synaptically-evoked muscarinic s-i.p.s.p. S A reversible AChE inhibitor, pyridostigmine (10-100gM), also depressed the amplitude and prolonged the duration of a muscarinic hyperpolarization induced by either preganglionic stimulation or ACh pressure application. These actions were reversible, and not accompanied by a significant change in membrane potential or input resistance.6 The inhibitory action of soman (1 yM) on the muscarinic hyperpolarization was prevented by pyridostigmine (1OgM), but not by atropine (1 pM).7 These results demonstrate that soman prolongs not only the muscarinic hyperpolarization, but also inhibits its amplitude through a postsynaptic action, probably through AChE inhibition, in cat bladder parasympathetic neurones.

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Global changes in the expression patterns of RNA isolated from the hippocampus and cortex of VX exposed mice

Blanton

D'Ambrozio

Sistrunk

et al. 2004

J Biochem & Molecular Tox

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One of the established activities of the nerve agent VX is inhibition of the enzyme acetylcholinesterase (AChE). This inhibition affects the cholinergic nervous system by decreasing the activity of the neurotransmitter-hydrolyzing enzyme cholinesterase (ChE). In an effort to gain a more comprehensive understanding of the molecular pathways affected by low-level exposure to VX, an expression profiling approach was used to identify genes with altered RNA expression patterns after exposure.Specifically, mice were exposed to 0.1, 0.2, 0.4, and 0.6 LD50 VX for a period of 2 weeks. At 2 h, 72 h, and 2 weeks after the final exposure, RNA was isolated from both the hippocampus and the cortex. Changes in gene expression levels were assessed by DNA microarray technology and grouped according to their expression patterns. Data presented here demonstrate that 2 weeks postexposure all up-regulated gene expression has returned to pre-exposure levels, including genes related to the central nervous system. Additionally, this investigation has revealed non-AChE pathway genes involved in other neuronal functions that display altered expression profiles after VX exposure.

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Activation and Blockade of the Nicotinic and Glutamatergic Synapses by Reversible and Irreversible Cholinesterase Inhibitors

Cited by 20 publications

References 35 publications

Molecular Targets and Synaptic Effects of Carbamates, Organophosphates, Oximes, and Pyridiniums: Implications for Prophylaxis and Therapy of Organophosphate Toxicity

Molecular Targets and Synaptic Effects of Carbamates, Organophosphates, Oximes, and Pyridiniums: Implications for Prophylaxis and Therapy of Organophosphate Toxicity

Action of an irreversible acetylcholine esterase inhibitor, soman, on muscarinic hyperpolarization in cat bladder parasympathetic ganglia

Global changes in the expression patterns of RNA isolated from the hippocampus and cortex of VX exposed mice

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