In Vivo and in Vitro Regional Differential Sensitivity of Neuropathy Target Esterase to Di-n-butyl-2,2-dichlorovinyl Phosphate

Overview

Journal Arch Toxicol

Specialty Toxicology

Date 1989 Jan 1

PMID 2619560

Citations 5

Authors

A Moretto

M Lotti

P S Spencer

Affiliations

Soon will be listed here.

Abstract

Organophosphate-induced delayed polyneuropathy (OPIDP) is initiated by inhibition/aging of more than 70-75% of neuropathy target esterase (NTE). Di-n-butyl-2,2-dichlorovinyl phosphate (DBDCVP) (1 mg/kg s.c.) inhibited 96%, 86% and 83% of NTE in brain, spinal cord and peripheral nerve, respectively, and induced a typical central peripheral distal axonopathy in hens. A lower dose (0.45 mg/kg s.c.) caused 90%, 83% and 54% NTE inhibition in the same organs; by contrast, hens developed a spastic ataxia with axonal degeneration in spinal cord but not in peripheral nerve. With a dose of 0.2 mg/kg s.c., a suprathreshold inhibition of NTE was produced in brain (78%) but not in spinal cord (56%) and peripheral nerve (33%) and no morphological or clinical signs of neuropathy developed in hens. With doses up to 4.0 mg/kg s.c., acetylcholinesterase (AChE) inhibition was similar throughout the nervous system. In vitro time-course inhibition studies showed a different sensitivity to DBDCVP of NTE from peripheral nerve (ka = 5.4 x 10(6)) relative to that from spinal cord (ka = 13.9 x 10(6)) or brain (ka = 20.6 x 10(6)). In vitro I50s of DBDCVP for AChE were similar in brain, spinal cord and peripheral nerve (11-17 nM). These data support the hypothesis that the critical target for initiation of OPIDP is located in the nerve fiber, possibly in the axon and also suggest that peripheral nerve NTE has a different sensitivity to DBDCVP than the brain enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Citing Articles

Triphenylphosphite neuropathy in hens.

Fioroni F, Moretto A, Lotti M Arch Toxicol. 1995; 69(10):705-11.

PMID: 8572929 DOI: 10.1007/s002040050236.

Organophosphate polyneuropathy and neuropathy target esterase: studies with methamidophos and its resolved optical isomers.

Lotti M, Moretto A, Bertolazzi M, Peraica M, Fioroni F Arch Toxicol. 1995; 69(5):330-6.

PMID: 7654138 DOI: 10.1007/s002040050179.

Interaction of methamidophos with hen and human acetylcholinesterase and neuropathy target esterase.

Bertolazzi M, Caroldi S, Moretto A, Lotti M Arch Toxicol. 1991; 65(7):580-5.

PMID: 1781739 DOI: 10.1007/BF01973720.

Chlorpyrifos-induced delayed polyneuropathy.

Capodicasa E, Scapellato M, Moretto A, Caroldi S, Lotti M Arch Toxicol. 1991; 65(2):150-5.

PMID: 1711837 DOI: 10.1007/BF02034943.

Phenylmethanesulfonyl fluoride elicits and intensifies the clinical expression of neuropathic insults.

Moretto A, Bertolazzi M, Capodicasa E, Peraica M, Richardson R, Scapellato M Arch Toxicol. 1992; 66(1):67-72.

PMID: 1316117 DOI: 10.1007/BF02307272.

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