Twitch potentiation by organophosphate anticholinesterases in rat phrenic nerve diaphragm preparations.
1 Twitch potentiation produced by anticholinesterases has been variously attributed to the prolonged postjunctional action of acetylcholine (ACh), a prejunctional action of ACh involving the initiation of antidromic firing (ADF) in the nerve or a direct action of the anticholinesterases on nerve terminals initiating ADF. 2 The organophosphate anticholinesterases, paraoxon (diethyl-4-nitrophenylphosphate) and DFP (diisopropyl fluorophosphate), when applied to rat isolated diaphragm preparations for 30 min, produced twitch potentiation which subsequently declined. 3 The rates of onset and decline of twitch potentiation were directly related to the concentration of the organophosphates and the reversibility of their effects was in line with the reactivation of the phosphorylated enzymes formed by them, whether reactivation was spontaneous or induced by the oxime, N,N'-trimethylene-1, 3-bis(pyridinium-4-aldoxime). 4 Reducing the output of ACh from nerve terminals (by reducing the ratio of calcium: magnesium ions in the bathing solution) or reducing the affinity of ACh for the nicotinic cholinoceptor (using the disulphide bond reducing agent, dithiothreitol) produced the same effects as did lowering the concentration of the organophosphates. 5 It is concluded that the twitch potentiation produced by paraoxon and DFP, and its failure to be maintained when the higher concentrations of the organophosphates were used, were the direct result of the excess of ACh in the synaptic cleft, following inhibition of acetylcholinesterase.
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003964:Diaphragm / Q000187:drug effects; D004229:Dithiothreitol / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009132:Muscles / Q000187:drug effects*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010791:Phrenic Nerve / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000187:drug effects
D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D011978:Receptors, Nicotinic; D000109:Acetylcholine; D004229:Dithiothreitol