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. 1989 May;97(1):65–70. doi: 10.1111/j.1476-5381.1989.tb11924.x

Prejunctional modulation of acetylcholine release from the skeletal neuromuscular junction: link between positive (nicotinic)- and negative (muscarinic)-feedback modulation.

E S Vizi 1, G T Somogyi 1
PMCID: PMC1854489  PMID: 2720313

Abstract

1. Presynaptic receptor-mediated modulation of stimulation-evoked [3H]-acetylcholine[( 3H]-ACh) release from the neuromuscular junction was studied in the region of the mouse hemidiaphragm which contains the motor endplates, and which can easily be loaded with [3H]-choline. This method made it possible to detect exclusively the [Ca2+]0-dependent, quantal release of [3H]-ACh in response to axonal stimulation. 2. Atropine enhanced, and non-depolarizing muscle relaxants [+)-tubocurarine, pancuronium and pipecuronium) reduced, the release of [3H]-ACh evoked by high frequency trains of stimulation (50 Hz, 40 shocks) of the phrenic nerve. The effect of (+)-tubocurarine was frequency-dependent as at 5 Hz (40 shocks) it was less effective than at 50 Hz. The resting release of [3H]-ACh was not affected by these compounds. These findings indicate that ACh released into the synaptic gap by axonal firing reaches a concentration sufficient to influence its own release by a prejunctional effect. 3. The anticholinesterase, physostigmine sulphate, enhanced the release of [3H]-ACh in a concentration-dependent manner. This effect was mediated via prejunctional nicotinic receptor stimulation: (+)-tubocurarine, pancuronium and pipecuronium completely prevented the effect of physostigmine. 4. When the prejunctional nicotinic and muscarinic receptors were stimulated by a high concentration of extracellular ACh which had accumulated in the junctional gap in the presence of physostigmine, atropine did not influence the evoked release of [3H]-ACh. However, when the effect of endogenous ACh on nicotinic receptors was prevented by (+)-tubocurarine, atropine enhanced the release.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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