Diaphragm acetylcholinesterase activity

Haigh, J.R., Johnston, S.R., Peters, B.M., et al, 2005. Inhibition of guinea pig hemi-diaphragm acetylcholinesterase activity by pyridostigmine bromide and protection against soman toxicity. Chem. Biol. Interact. 157-158,381-382. 

In dogs poisoned with soman (Intravenously at 30 pg/kg) and treated with I at 104 mg/kg (Intravenously 31/2 min after soman), the large dose of I stopped aging of Inhibited cholinesterase and reactivated 24.0% and 35.6% of the red-cell and diaphragm cholinesterase activities, respectively. It failed to reactivate brain cholinesterase. Indeed, the brain acetylcholinesterase activity after the treatment with 1 was lower than that just before the injection of I. The last finding indicates the inability of I to cross the blood-brain barrier in significant quantities. 

Thiermarm, FI., Worek, F., Szinicz, L., Zilker, T., Eyer, P. (2002). Acetylcholinesterase activity and muscle function in mouse diaphragm preparation and organophosphate patients. The meeting of NATO TG 004 Task Group on Prophylaxis and Therapy of Chemical Agents. November 4-7, 2002, Oslo, Norway. 

The function of acetylcholinesterase (AChE) is to degrade the neurotransmitter acetylcholine (ACh). "niere is general agreement that the acute toxicity of OP is explained by irreversible inhibition of AChE activity at cholinergic synapses (Chambers and Levi, 1992 McDonough and Shih, 1997 Mileson etal., 1998 Pope, 1999 Taylor, 2001 Casida and Quistad, 2004). Inhibition of AChE (>70%) leads to accumulation of ACh at central and peripheral sites. In the brain, overstimulation of ACh receptors can lead to seizures. Inhibition of the breathing center in the brain results in asphyxiation. In the diaphragm muscle, overstimulation of... 

A practical detail, useful in recognizing the receptor, is that the Formosan snake toxin, a-bungarotoxin (acetyl- W) binds only to the acetylcholine (ACh) receptor site (in mouse diaphragm muscle), whereas diwopropyl-phosphorofluoridate ( H) 12,15) binds specifically to the active site of acetylcholinesterase. An equal number (3 x 10 per end-plate) of the receptor and the enzyme sites is found, i.e. one active molecule per 5000 A of the membrane, which is consequently densely occupied by these two proteins. Blockade becomes marked only when 70 per cent of the ACh receptor sites are occupied, and hence there are not many spare receptors at this site (Barnard, Wieckowski, and Chiu, 1971). 

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