Noradrenergic-mediated potentiation of acetylcholine release from the phrenic nerve: Evidence for presynaptic α1-adrenoceptor involvement

Abstract

This study, conducted in the rat phrenic nerve-diaphragm preparation, was designed to establish more direct evidence that norepinephrine enhances acetylcholine (ACh) release from motor neurons and characterize the α-adrenoceptor type mediating this action. Norepinephrine (50 μM, α 1 + α 2 agonist) increased nerve-stimulated release by 183%, as determined by radioenzymatic assay. This effect was completely abolished by pretreatment with the α-adrenoceptor antagonists phentolamine ( α 1 + α 2) and by WB 4101 ( α 1) but only modestly reduced by yohimbine ( α 2). Clonidine ( α 2 agonist) did not enhance ACh release or nerve-stimulated muscle contractions, while phenylephrine ( α 1 agonist) and norepinephrine increased muscle contractions up to 19.5–22.4%. These results support the hypothesis that norepinephrine increases ACh release from somatic motor nerves via a presynaptic α 1 interaction.