title: Diisopropylphosphorofluoridate-induced depression of compound action potential of frog sciatic nerve in vitro is mediated through the inhibition of cholinesterase activity.
abstract: 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 microM DFP produced a 5% depression (P < 0.05) and the maximal depression (30% of control) was observed with 1 microM. The SPK-3 (up to 10 microM) had no effect on the CAP; SPK-3 (10 microM) antagonized the DFP-induced depression of the CAP partially but not after 1 microM DFP. However, the inhibitory concentration of DFP to produce 50% of the maximal depression (IC50) was 0.38 +/- 0.025 microM in the presence of SPK-3 (10 microM; n = 4), against 0.15 +/- 0.05 microM for DFP alone (n = 7). These IC50 values were significantly different (P < 0.05, Student's t-test). The DFP decreased nerve ChE activity by 41% in the 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.
authors.affiliation: Department of Physiology, Banaras Hindu University, Varanasi, India.
authors.forename: S B
authors.initials: SB
authors.lastname: Deshpande
authors.forename: P
authors.initials: P
authors.lastname: Kumar
authors.forename: A S
authors.initials: AS
authors.lastname: Sachan
authors.forename: S N
authors.initials: SN
authors.lastname: Dube
authors.forename: S
authors.initials: S
authors.lastname: Das Gupta
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D015536:Down-Regulation; D066298:In Vitro Techniques; D007531:Isoflurophate / Q000633:toxicity*; D011726:Pyridinium Compounds / Q000494:pharmacology; D011898:Ranidae; D012584:Sciatic Nerve / Q000187:drug effects*
chemical_list: D002800:Cholinesterase Inhibitors; D011726:Pyridinium Compounds; C104222:SPK 3; D007531:Isoflurophate