Recovery of acetylcholinesterase and of its multiple molecular forms in motor end-plate-free and motor end-plate-rich regions of mouse striated muscle, after irreversible inactivation by an organophosphorus compound (methyl-phosphorothiolate derivative).
Most of mouse diaphragm muscle acetylcholinesterase (AChE) is irreversibly inhibited after a single intraperitoneal injection of a methyl-phosphorothiolate derivative (MPT), an organophosphorus compound which phosphorylates the active site. The muscle recovers its AChE (de novo synthesis) and we studied the time course of reappearance of AChE and its multiple active molecular forms. After inhibition, there is an initial (3 to 15 hr) rapid recovery of total AChE (which evolves from 20-28% to 50-60% of the control values), followed by a slow phase of AChE return. After 3 days, the recovery is still incomplete (reaching 70-80% of control values). Among the main molecular forms present in diaphragm muscle (16 S, 10 S and 4 S, accompanied by minor components), the 16 S and 10 S forms are the most sensitive to MPT treatment. During the rapid initial phase of AChE recovery, the absolute rate of recovery of the 4 S form is faster than for the other forms with a correspondingly much higher relative proportion to total AChE. These observations are consistent with the hypothesized precursor role of the 4 S form. The 16 S form, which is found concentrated in the motor end-plate (MEP)-rich regions and in low amounts in MEP-free regions, is similarly partially recovered in both regions, suggesting that there is 16 S biosynthesis not only in the MEP-rich regions but also in the MEP-free regions.
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002801:Cholinesterase Reactivators; D003964:Diaphragm / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D009045:Motor Endplate / Q000201:enzymology*; D009132:Muscles / Q000201:enzymology; D009469:Neuromuscular Junction / Q000201:enzymology*; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*
D000110:Acetylcholinesterase; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D009946:Organothiophosphorus Compounds; C009680:VX-agent