Noradrenergic-mediated potentiation of acetylcholine release from the phrenic nerve: evidence for presynaptic alpha 1-adrenoceptor involvement |
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Authors: | R M Snider M C Gerald |
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Affiliation: | Division of Pharmacology, College of Pharmacy The Ohio State University Columbus, Ohio 43210, USA |
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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 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. |
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Keywords: | To whom correspondence should be addressed. |
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