Potentiation of the response of frog rectus muscle to acetylcholine by isopropyl methyl phosphonofluoridate and its modification by pyridine-2-aldoxime methiodide.

Abstract

Pyridine-2-aldoxime methiodide (P2AM) was used to study the relation between the recovery of cholinesterase activity of isolated frog rectus abdominis muscle and the change of isotonic response to acetylcholine after previous treatment with the anticholinesterase, isopropyl methyl phosphonofluoridate (sarin). Addition of P2AM to muscle which had been incubated with sarin produced an 88% decrease in potentiation to acetylcholine. This was accompanied by 71% and 35% recoveries of the cholinesterase activity of the intact and finely ground muscle respectively compared with controls from the contralateral muscle. Following pre-treatment with sarin, a two-hour rinsing with acetylcholine (3 mug./ml.) produced a 61% decrease in potentiation to acetylcholine accompanied by 24% and 4.5% recoveries of cholinesterase activity in intact and in ground muscle respectively. Since control experiments showed absence of uncombined sarin in the muscle after rinsing with acetylcholine solution, the results indicate a greater effectiveness of P2AM and acetylcholine in reactivating superficially situated cholinesterase of the frog rectus abdominis as compared with enzyme within the interior of the muscle.