Contribution of de novo synthesis of acetylcholinesterase to spontaneous recovery of neuromuscular transmission following soman intoxication

Dongen, C.J. van; Valkenburg, P.W.; Helden, H.P.M. van

doi:10.1016/0014-2999(88)90673-5

Cited by 10 publications

(3 citation statements)

References 10 publications

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“…After washout of soman, the amplitude of the muscarinic hyperpolarization partially recovered, although the duration remained prolonged. This finding is consistent with observations of spontaneous recovery of ganglionic (Lukomskaya et al, 1980) or neuromuscular (Van Dongen et al, 1988) transmission following treatment with irreversible AChE inhibitors. Recovery from soman treatment may occur through an unknown mechanism independent of de novo synthesis of AChE.…”

Section: Recovery From Soman Actionsupporting

confidence: 92%

“…When soman was applied to bladder neurones a second time, the partially-recovered muscarinic response was not depressed further. The lack of an effect of a second application of organophosphorus AChE inhibitors has also been demonstrated for EEG seizure elicited by DFP in rabbits (Van Meter et al, 1978) and for inhibition of neuromuscular transmission by soman in rats (Van Dongen et al, 1988). These data also suggest that the soman-induced depression of the muscarinic hyperpolarization in bladder neurones is due to inhibition of AChE.…”

Section: Recovery From Soman Actionsupporting

confidence: 63%

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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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Section: Recovery From Soman Actionsupporting

confidence: 92%

Section: Recovery From Soman Actionsupporting

confidence: 63%

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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“…, 1953; Wright, 1954). When animals were maintained alive by artificial ventilation, respiratory activity and neuromuscular transmission recovered within a few hours (Meeter & Wolthuis, 1968; Melchers & van der Laaken, 1991), a delay much too short to allow any significant de novo synthesis of the enzyme (Van Dongen et al. , 1988).…”

Section: Discussionmentioning

confidence: 99%

Respiratory survival mechanisms in acetylcholinesterase knockout mouse

Chatonnet

Boudinot

Chatonnet³

et al. 2003

Eur J of Neuroscience

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Cholinergic neurotransmission ensures muscle contraction and plays a role in the regulation of respiratory pattern in the brainstem. Inactivation of acetylcholinesterase (AChE) by organophosphates produces respiratory failure but AChE knockout mice survive to adulthood. Respiratory adaptation mechanisms which ensure survival of these mice were examined in vivo by whole body plethysmography and in vitro in the neonatal isolated brainstem preparation. AChE-/- mice presented no AChE activity but unaffected butyrylcholinesterase (BChE) activity. In vivo, bambuterol (50-500 microg/kg s.c.) decreased BChE activity peripherally but not in brain tissue and induced apnea and death in adult and neonate AChE-/- mice without affecting littermate AChE+/+ and +/- animals. In vitro, bath-applied bambuterol (1-100 microm) and tetraisopropylpyrophosphoramide (10-100 microm) decreased BChE activity in the brainstem but did not perturb central respiratory activity recorded from spinal nerve rootlets. In vitro, the cholinergic agonists muscarine (50-100 microm) and nicotine (0.5-10 microm) induced tonic activity in respiratory motoneurons and increased the frequency of inspiratory bursts in AChE+/+ and +/- animals. These effects were greatly attenuated in AChE-/- animals. The results suggest that, in mice lacking AChE, (i) BChE becomes essential for survival peripherally but plays no critical role in central rhythm-generating structures and (ii) a major adaptive mechanism for respiratory survival is the down-regulated response of central respiratory-related neurons and motoneurons to muscarinic and nicotinic agonists.

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The functional role of molecular forms of acetylcholinesterase in neuromuscular transmission

Busker

Wiel

et al. 1994

Neurochem Res

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The severity of poisoning following acetylcholinesterase (AChE) inhibition correlates weakly with total AChE activity. This may be partly due to the existence of functional and non-functional pools of AChE. AChE consists of several molecular forms. The aim of the present study was to investigate which of these forms will correlate best with neuromuscular transmission (NMT) remaining after partial inhibition of this enzyme. Following sublethal intoxication of rats with the irreversible AChE inhibitor soman, diaphragms were isolated after 0.5 or 3 h. It appeared that at 3 h after soman poisoning the percentage of G1 increased, while those of G4 and A12 decreased. NMT was inhibited more strongly than in preparations obtained from the 0.5 h rats with the same level of AChE inhibition, but with a normal ratio of molecular forms. NMT correlated positively with G4 as well as with A12, but inversely with G1. In vitro inhibition with the charged inhibitors DEMP and echothiophate resulted in higher levels of total AChE, relatively less G1 and more G4 and A12 than after incubation with soman, but led to less NMT. Treatment of soman-intoxicated rats with the reactivating compound HI-6 resulted in preferential reactivation of A12, persisting low levels of G1 and concurrent recovery of NMT as compared with saline-treated soman controls with equal total AChE activity. Apparently, in rat diaphragm G4 and A12 are the functional AChE forms.

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Contribution of de novo synthesis of acetylcholinesterase to spontaneous recovery of neuromuscular transmission following soman intoxication

Cited by 10 publications

References 10 publications

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

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

Respiratory survival mechanisms in acetylcholinesterase knockout mouse

The functional role of molecular forms of acetylcholinesterase in neuromuscular transmission

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