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Diisopropylphosphorofluoridate‐induced Depression of Compound Action Potential of Frog Sciatic Nerve in vitro is Mediated Through the Inhibition of Cholinesterase Activity
Author(s) -
Deshpande S.B.,
Kumar P.,
Sachan A.S.,
Dube S.N.,
Gupta S. Das
Publication year - 1996
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/(sici)1099-1263(199611)16:6<497::aid-jat381>3.0.co;2-y
Subject(s) - cholinesterase , pharmacology , chemistry , sciatic nerve , in vitro , ic50 , endocrinology , medicine , anesthesia , biochemistry
Effect of diisopropylphosphorofluoridate (DFP), an irreversible cholinesterase (ChE) inhibitor, on compound action potential (CAP) of sciatic nerve in vitro was examined. Further, the role of cholinesterase reactivator (1 acetyl‐4‐hydroxy imino methyl pyridinium bromide; SPK‐3) in reversing DFP‐induced changes was also evaluated. Diisopropylphosphorofluoridate produced a dose‐dependent depression of the CAP. A concentration as low as 0.01 μM DFP produced a 5% depression ( P < 0.05) and the maximal depression (30% of control) was observed with 1 μM. The SPK‐3 (up to 10 μM) had no effect on the CAP; SPK‐3 (10 μM) antagonized the DFP‐induced depression of the CAP partially but not after 1 μM DFP. However, the inhibitory concentration of DFP to produce 50% of the maximal depression (ic 50 ) was 0.38 ± 0.025 μM in the presence of SPK‐3 (10 μM; n = 4), against 0.15 ± 0.05 μM for DFP alone ( n = 7).These ic 50 values were significantly different ( P < 0.05, Student's t ‐test). The DFP decreased nerve ChE activity by 41% in t he absence of SPK‐3 and by 31% in the presence of SPK‐3. Although SPK‐3 could not completely reactivate the inhibited enzyme, it seems reasonable to conclude that the DFP‐induced depression of the action potential of sciatic nerve was mediated by inhibiting the ChE activity.