PMID: 8584654Jan 1, 1995Paper

Metabolism of agmatine (clonidine-displacing substance) by diamine oxidase and the possible implications for studies of imidazoline receptors

Progress in Brain Research
A Holt, G B Baker

Abstract

Clonidine-displacing substance, thought to be the endogenous ligand for imidazoline receptors, has been identified recently as agmatine (1-amino-4-guanidinobutane). The similarity of this compound's structure to that of the diamine oxidase (DAO) inhibitor, aminoguanidine, led us to investigate the possibility that agmatine might be a substrate for this enzyme. The metabolism of agmatine by purified porcine kidney DAO was measured by a peroxidase-linked colorimetric assay. Agmatine was a substrate for this enzyme and, under the experimental conditions used here, was metabolised at a rate of 0.8 mumol agmatine h-1 (unit DAO activity)-1. In contrast, agmatine was a substrate neither for rat brain monoamine oxidase (MAO) -A or -B, nor for rat brown adipose tissue semicarbazide-sensitive amine oxidase (SSAO). The metabolism of agmatine by DAO was inhibited by aminoguanidine (IC50 14.9 nM) and by the antidepressant, phenelzine (IC50 1.95 microM). These results suggest that administration of DAO inhibitors may increase endogenous agmatine levels and thus alter imidazoline receptor densities. A review of the literature documenting ligand affinities for idazoxan-preferring (I2) imidazoline binding site subtypes and drug affinities for D...Continue Reading

Citations

Jul 27, 2001·Journal of Cellular Physiology·J SatrianoR C Blantz
Jul 27, 2007·Cellular and Molecular Neurobiology·Ning WuJin Li
Apr 2, 2008·Journal of Neural Transmission·Jarogniew J LuszczkiStanislaw J Czuczwar
Sep 4, 2015·Journal of Pharmacokinetics and Pharmacodynamics·Sook Wah YeeKathleen M Giacomini
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Jul 28, 2017·The Biochemical Journal·Gregor Laube, Hans-Gert Bernstein
Mar 28, 2019·Bioscience Reports·Radka KončitíkováDavid Kopečný
May 16, 2009·Pharmacological Reports : PR·Jarogniew J LuszczkiStanisław J Czuczwar
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Jun 11, 2011·Chemical Reviews·Daniele CastagnoloMaurizio Botta

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