Agmatine, a bioactive metabolite of arginine. Production, degradation, and functional effects in the kidney of the rat.

Abstract

Until recently, conversion of arginine to agmatine by arginine decarboxylase (ADC) was considered important only in plants and bacteria. In the following, we demonstrate ADC activity in the membrane-enriched fraction of brain, liver, and kidney cortex and medulla by radiochemical assay. Diamine oxidase, an enzyme shown here to metabolize agmatine, was localized by immunohistochemistry in kidney glomeruli and other nonrenal cells. Production of labeled agmatine, citrulline, and ornithine from [3 H]arginine was demonstrated and endogenous agmatine levels (10 Ϫ 6 M) in plasma ultrafiltrate and kidney were measured by HPLC. Microperfusion of agmatine into renal interstitium and into the urinary space of surface glomeruli of Wistar-Frömter rats produced reversible increases in nephron filtration rate (SNGFR) and absolute proximal reabsorption (APR). Renal denervation did not alter SNGFR effects but prevented APR changes. Yohimbine (an ␣ 2 antagonist) microperfusion into the urinary space produced opposite effects to that of agmatine. Microperfusion of urinary space with BU-224 ( M), a synthetic imidazoline 2 (I 2 ) agonist, duplicated agmatine effects on SNGFR but not APR whereas an I 1 agonist had no effect. Agmatine effects on SNGFR and APR are not only dissociable but appear to be mediated by different mechanisms. The production and degradation of this biologically active substance derived from arginine constitutes a novel endogenous regulatory system in the kidney. ( J. Clin. Invest. 1996. 97:413-420.)

Arginine metabolism: nitric oxide and beyond

“…However, arginine decarboxylase activity and agmatine synthesis have now been identified in brain, liver, kidney, adrenal gland, macrophages and small intestine [271][272][273][274]. This enzyme is localized within the mitochondrial fraction of cell homogenates [272,275].…”

“…Although the physiological roles of agmatine are still under investigation [273,276,277], three lines of investigation have suggested possible functions of this arginine metabolite. Agmatine binds to α # -adrenergic and imidazoline receptors [271], suggesting a role in cell signalling.…”

Effect of agmatine on the blood system parameters of rats under the condition of experimental diabetes mellitus

“…У роботі було використано продукт декарбоксилювання аргініну -катіонний полі-амін агматин, який поширений у різних типах клітин і тканин та виконує цілу низку важливих фізіологічних функцій [13]. Агматин в організмі діє як нейротрансмітер і нейромодулятор, є ендогенним лігандом для імідазольних рецепторів (І 1 /І 2 ) і, з меншою афінністю, для α 2 -адренорецепторів, N-метил-D-аспартат і серотоніно-вих рецепторів [15].…”

Agmatine Suppresses Mesangial Cell Proliferation by Modulating Polyamine Metabolism

“…The kidney is unusual in displaying high constitutive ADC activity, and may be a principal contributor of systemic agmatine (Lortie et al 1996). Agmatine has the capacity to regulate nitric oxide (NO) synthase activity (Galea et al 1996;Abe et al 2000;Satriano et al 2001a) and has been ascribed roles in association with neurotransmitter receptors (Li et al 1994), modulation of opioid analgesia (Kolesnikov et al 1996), and as an ADP-ribose acceptor (Murayama et al 1993).…”