Journal
NEUROPHARMACOLOGY
Volume 47, Issue 3, Pages 438-449Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2004.04.017
Keywords
adrenergic receptor; norepinephrine; dopamine; octopamine; tyramine; mouse
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The adrenergic system is a neuromodulatory system whose endogenous ligands are considered to be the catecholamines norepinephrine (NE) and epinephrine (E). Evidence suggests that the catecholamine dopamine (DA) may also activate adrenergic signaling. Further, tyramine (TA) and octopamine (OA) are other monoamines that can be produced in catecholaminergic cells when tyrosine hydroxylase activity is low or absent, as in some genetic mouse models of adrenergic function. Here, we systematically examine the ability of these L-tyrosine-derived monoamines to activate all 10 known isoforms of the cloned mouse adrenergic receptors expressed in Chinese hamster ovary cells. In comparison to NE or E, DA is nearly as efficacious in this system but is from 1 to 4 orders of magnitude less potent. In comparison to DA, OA has roughly equivalent potency but is usually only a partial agonist. TA is either very weak or lacks agonism. Of note, all three mouse alpha(1) receptors increase cAMP, in contrast to results reported for human alpha(1d) receptors. In addition, a 12-amino acid hemagglutinin epitope tag added to the N-terminus of alpha(2) receptors selectively enhances the potency of NE similar to10- to 100-fold, indicating that caution should be applied when interpreting physiological results from experiments using modified receptors. (C) 2004 Elsevier Ltd. All rights reserved.
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