Stimulation of alpha 1-adrenoceptors increases electrically evoked [3H]acetylcholine release from the rat phrenic nerve.

The modulation by sympathomimetic amines of the electrically evoked [3H]acetylcholine release from the motor nerve was investigated. Phenylephrine (10 mumol/l), alpha-methylnoradrenaline (10 mumol/l) and adrenaline (1 mumol/l) enhanced the electrically evoked [3H]acetylcholine release from the rat phrenic nerve. The enhancing effect of phenylephrine was completely prevented by low concentrations of prazosin (0.1 or 0.01 mumol/l) whereas a high concentration of yohimbine (1 mumol/l) was necessary to abolish the effect of phenylephrine. The simultaneous blockade of alpha- and beta-adrenoceptors, i.e. propranolol (0.1 mumol/l) together with prazosin (0.01 mumol/l) or yohimbine (1 mumol/l), was required to abolish the enhancing effect of alpha-methylnoradrenaline. Likewise, the enhancing effect of adrenaline could be abolished only by a combination of two antagonists (propranolol together with yohimbine or prazosin). Neither clonidine nor oxymetazoline (1 or 10 mumol/l) modulated the evoked [3H]acetylcholine release. The experiments showed the existence of alpha-adrenoceptors which are present on the motor nerve and whose stimulation mediates an increase in evoked transmitter release. The different potencies found for prazosin and yohimbine indicate that an alpha 1-subtype of the receptors was involved. Increased sympathetic activity may facilitate neuromuscular transmission by stimulation of presynaptic alpha- and beta-adrenoceptors.