title: Regulation of acetylcholinesterase activity by nitric oxide in rat neuromuscular junction via N-methyl-D-aspartate receptor activation.
abstract: Acetylcholinesterase (AChE) is an enzyme that hydrolyses the neurotransmitter acetylcholine, thereby limiting spillover and duration of action. This study demonstrates the existence of an endogenous mechanism for the regulation of synaptic AChE activity. At the rat extensor digitorum longus neuromuscular junction, activation of N-methyl-d-aspartate (NMDA) receptors by combined application of glutamate and glycine led to enhancement of nitric oxide (NO) production, resulting in partial AChE inhibition. Partial AChE inhibition was measured using increases in miniature endplate current amplitude. AChE inhibition by paraoxon, inactivation of NO synthase by N(x)-nitro-L-arginine methyl ester, and NMDA receptor blockade by DL-2-amino-5-phosphopentanoic acid prevented the increase in miniature endplate current amplitude caused by amino acids. High-frequency (10 Hz) motor nerve stimulation in a glycine-containing bathing solution also resulted in an increase in the amplitude of miniature endplate currents recorded during the interstimulus intervals. Pretreatment with an NO synthase inhibitor and NMDA receptor blockade fully eliminated this effect. This suggests that endogenous glutamate, released into the synaptic cleft as a co-mediator of acetylcholine, is capable of triggering the NMDA receptor/NO synthase-mediated pathway that modulates synaptic AChE activity. Therefore, in addition to well-established modes of synaptic plasticity (e.g. changes in the effectiveness of neurotransmitter release and/or the sensitivity of the postsynaptic membrane), another mechanism exists based on the prompt regulation of AChE activity.
authors.affiliation: Kazan Institute of Biochemistry and Biophysics, Russian Academy of Sciences, PO Box 30, Kazan 420111, Russia. kpetrov2005@mail.ru
authors.forename: Konstantin A
authors.initials: KA
authors.lastname: Petrov
authors.forename: Artem I
authors.initials: AI
authors.lastname: Malomouzh
authors.forename: Irina V
authors.initials: IV
authors.lastname: Kovyazina
authors.forename: Eric
authors.initials: E
authors.lastname: Krejci
authors.forename: Alexandra D
authors.initials: AD
authors.lastname: Nikitashina
authors.forename: Svetlana E
authors.initials: SE
authors.lastname: Proskurina
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Zobov
authors.forename: Evgeny E
authors.initials: EE
authors.lastname: Nikolsky
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D055369:Miniature Postsynaptic Potentials; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000378:metabolism* / Q000502:physiology; D009473:Neuronal Plasticity; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010261:Paraoxon / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D002800:Cholinesterase Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D018698:Glutamic Acid; C056639:2-amino-5-phosphopentanoic acid; D019001:Nitric Oxide Synthase; D000110:Acetylcholinesterase; D014633:Valine; D010261:Paraoxon; D019331:NG-Nitroarginine Methyl Ester