Diisopropylphosphorofluoridate-induced depression of compound action potential of frog sciatic nerve in vitro is mediated through the inhibition of cholinesterase activity.
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.
Deshpande
S B
SB
Department of Physiology, Banaras Hindu University, Varanasi, India.
Kumar
P
P
Sachan
A S
AS
Dube
S N
SN
Das Gupta
S
S
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*
D002800:Cholinesterase Inhibitors; D011726:Pyridinium Compounds; C104222:SPK 3; D007531:Isoflurophate