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

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 studies.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 mug/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 alpha-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.