Effect of frequency of stimulation on the inhibition by noradrenaline of the acetylcholine output from parasympathetic nerve terminals

Abstract

1 The relationship between the number of shocks delivered, the frequency of stimulation and the acetylcholine output per volley from nerve terminals of the longitudinal muscle strip of the guinea-pig ileum was studied. 2 There was an inverse correlation between acetylcholine output per volley and the frequency of stimulation when the same number of shocks was applied in each train. 3 With sustained stimulation, the volley output declined more rapidly the higher the frequency of stimulation. There was no decrease in volley output (11·7 (ng/g)/volley) when the frequency applied was 0·1 Hz or less. 4 Noradrenaline (10⁻⁶ g/ml) reduced the acetylcholine output per volley to the level produced by sustained stimulation at 10 Hz (1·4–1·9 (ng/g)/volley). The acetylcholine output following application of the first shocks of a train at high frequency stimulation was much reduced by noradrenaline as the output was higher than 1·4–1·9 (ng/g)/volley. This action of noradrenaline was antagonized by phentolamine (2 μg/ml for 20 min). 5 Amphetamine and methylamphetamine, which release NA from sympathetic nerve terminals, were active in reducing the acetylcholine output to low frequency parasympathetic nerve stimulation. Reserpine and α-methyl-p-tyrosine pretreatment prevented the effect of amphetamine and reduced that of methylamphetamine. 6 The fact that addition or release of noradrenaline, reduced acetylcholine output when the firing rate was high but short in duration, suggests that noradrenaline plays a general modulator role in controlling the output of acetylcholine from the parasympathetic nerve terminals.