Acetylcholine hydrolysis during neuromuscular transmission in the synaptic cleft of skeletal muscle of mouse and chick.
Inhibition of acetylcholinesterase (AChE) by more than 80% by neostigmine or physostigmine resulted in a failure of tetanic contraction (100 Hz) in the isolated mouse nerve-diaphragm preparation. In the chick biventer cervicis muscle, however, the tetanic contraction was well maintained and even outlasted the period of nerve stimulation after inactivation of AChE. The concentration of (+)tubocurarine for 70% block of the indirect twitch response of the mouse diaphragm at 0.1 Hz was increased from 0.67 to 0.99 to 1.21-2.03 microM in the presence of neostigmine (0.15-1.5 microM) which inhibited AChE by 70% or more, while that to depress the tetanic contraction (50 Hz) was increased from 0.38 to 0.42 to 0.53-0.69 microM. In the chick muscle, physostigmine at 2.4 microM increased the concentration of (+)tubocurarine for 70% block of the twitch response from 1.68 to 4.14 microM, whereas that for block of the response to exogenous acetylcholine (ACh) was increased from 1.47 to 74.6 microM. On single stimulation, the relative peak concentrations of acetylcholine (ACh) at the postsynaptic receptor site of the mouse diaphragm and chick biventer cervicis were estimated to be increased by about 110 and 120% respectively, after complete inhibition of AChE. In the chick muscle, physostigmine increased the relative concentration of ACh by about 40-fold at the receptor site for exogenously applied ACh. It is concluded that the intrinsic ACh released from the nerve terminal is hydrolyzed by about 50% during the time of diffusion across the synaptic cleft whereas most of exogenous ACh is hydrolyzed before reaching the target.
Chang
C C
CC
Hong
S J
SJ
Lin
H L
HL
Su
M J
MJ
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002645:Chickens; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009132:Muscles / Q000378:metabolism*; D009388:Neostigmine / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000378:metabolism*; D010830:Physostigmine / Q000494:pharmacology; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D014403:Tubocurarine / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D009388:Neostigmine; D010830:Physostigmine; D000109:Acetylcholine; D014403:Tubocurarine