Noradrenergic-mediated potentiation of acetylcholine release from the phrenic nerve: evidence for presynaptic alpha 1-adrenoceptor involvement.
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 alpha-adrenoceptor type mediating this action. Norepinephrine (50 microM, alpha 1 + alpha 2 agonist) increased nerve-stimulated release by 183%, as determined by radioenzymatic assay. This effect was completely abolished by pretreatment with the alpha-adrenoceptor antagonists phentolamine (alpha 1 + alpha 2) and by WB 4101 (alpha 1) but only modestly reduced by yohimbine (alpha 2). Clonidine (alpha 2 agonist) did not enhance ACh release or nerve-stimulated muscle contractions, while phenylephrine (alpha 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 alpha 1 interaction.
D000109:Acetylcholine / Q000378:metabolism*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010791:Phrenic Nerve / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D015016:Yohimbine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine; D000109:Acetylcholine; D009638:Norepinephrine; D010646:Phentolamine