AGMATINE, A BIOACTIVE METABOLITE OF ARGININE - PRODUCTION, DEGRADATION, AND FUNCTIONAL-EFFECTS IN THE KIDNEY OF THE RAT

Until recently, conversion of arginine to agmatine by arginine decarbo xylase (ADC) was considered important only in plants and bacteria. In the following, we demonstrate ADC activity in the membrane-enriched fr action 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 no nrenal cells. Production of labeled agmatine, citrulline, and ornithin e from [H-3]arginine was demonstrated and endogenous agmatine levels ( 10(-6) M) in plasma ultrafiltrate and kidney were measured by HPLC. Mi croperfusion of agmatine into renal interstitium and into the urinary space of surface glomeruli of Wistar-Fromter rats produced reversible increases in nephron filtration rate (SNGFR) and absolute proximal rea bsorption (APR). Renal denervation did not alter SNGFR effects but pre vented APR changes. Yohimbine (an alpha(2) antagonist) microperfusion into the urinary space produced opposite effects to that of agmatine. Microperfusion of urinary space with BU-224 (mu M), a synthetic imidaz oline(2) (I-2) agonist, duplicated agmatine effects on SNGFR but not A PR 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 m echanisms. The production and degradation of this biologically active substance derived from arginine constitutes a novel endogenous regulat ory system in the kidney.