Succinylcholine-induced acceleration and suppression of electrically evoked acetylcholine release from mouse phrenic nerve-hemidiaphragm muscle preparation.
The effects of a depolarizing neuromuscular blocker on electrically evoked acetylcholine (ACh) release were studied using a mouse phrenic nerve-diaphragm muscle preparation preloaded with [3H]-choline, and the changes in muscle tension were recorded simultaneously. Succinylcholine at a low concentration (1 microM) enhanced evoked [3H]-ACh release, which tended to follow the increase in peak amplitude of tetanic tension; whereas at high concentrations (10 and 30 microM), it simultaneously reduced both release and tension. Decamethonium even at 10 and 30 microM had little effect on [3H]-ACh release despite producing a significantly greater reduction in tension compared with succinylcholine. (+)-Tubocurarine (5 microM) prevented the enhancing effect of [3H]-ACh release induced by 1 microM, but not the decreasing effect induced by 10 microM succinylcholine. These results suggest that succinylcholine induced acceleration at low concentrations due to a positive feedback mechanism through presynaptic nicotinic ACh receptors and the inhibition of ACh release at high concentration contributes in part to the neuromuscular blockade.
Kimura
I
I
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Okazaki
M
M
Uwano
T
T
Kobayashi
S
S
Kimura
M
M
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D003650:Decamethonium Compounds / Q000494:pharmacology; D003964:Diaphragm / Q000294:innervation; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D010791:Phrenic Nerve / Q000187:drug effects / Q000378:metabolism*; D011863:Radioimmunoassay; D013390:Succinylcholine / Q000494:pharmacology*; D014316:Tritium; D014403:Tubocurarine / Q000494:pharmacology
D003650:Decamethonium Compounds; D014316:Tritium; C033019:decamethonium; D013390:Succinylcholine; D000109:Acetylcholine; D014403:Tubocurarine