Evidence that catecholamines increase acetylcholine release from neuromuscular junction through stimulation of alpha-1 adrenoceptors.

1. The effects of alpha-1 adrenoceptor agonists on 3H-acetylcholine release from mouse phrenic nerve-hemidiaphragm preparation were studied. 2. In preparation which had been incubated with 3H-choline, electrical stimulation (50 Hz, 0.8 s trains every 10 s) released 3H-acetylcholine. Neurochemical evidence was obtained that noradrenaline, adrenaline and phenylephrine facilitated the stimulation evoked release of 3H-acetylcholine. This effect was much more marked when the prejunctional nicotinic receptors mediating positive feedback modulation were blocked by (+)-tubocurarine. In the presence of this drug, when the release of 3H-acetylcholine was reduced, alpha-1 adrenoceptor agonists enhanced the release in a prazosin-sensitive manner. 3. The rank order of potency of alpha-1 adrenoceptor agonists was adrenaline greater than noradrenaline greater than phenylephrine. By contrast, methoxamine had no effect on the release of 3H-acetylcholine. It is suggested, therefore, that circulating catecholamines may be able to affect neuromuscular transmission through stimulation of presynaptic alpha-1 adrenoceptors.