Agmatine inhibits arginine vasopressin-stimulated urea transport in the rat inner medullary collecting duct

Abstract

Background. Agmatine, a putative endogenous ligand for imidazoline receptors, induces numerous biological effects. The agonist clonidine binds to alpha-2 (α2) adrenoceptors and imidazoline receptors, and inhibits arginine vasopressin (AVP)-stimulated urea permeability (Pu) in the rat inner medullary collecting duct (IMCD). Dexmedetomidine, a selective α2 agonist, does not inhibit AVP-stimulated Pu. This study was conducted to determine if agmatine affects Pu in the rat IMCD)and to investigate the possibility of an imidazoline-mediated mechanism. Methods. The isolated-perfused tubule technique was used to measure Pu in IMCDs from Wistar rats. AVP at 220 pmol/L or 8-chlorophenylthio cyclic adenosine monophosphate (8CPT cAMP) was used to stimulate Pu. Agmatine and other agents were added to the bath. Results. Agmatine at 1 μmol/L inhibited AVP-stimulated Pu by 50%. Agmatine-induced inhibition could not be separated completely from inhibition produced by the non-imidazoline, catecholamine epinephrine. Of three antagonists selective for α2 adrenoceptors (rauwolscine, yohimbine, and RX821002), only rauwolscine reversed inhibition, whereas each of the three imidazoline-selective antagonists tested (atipamezole, idazoxan, and BU239) produced a significant reversal. Agmatine did not affect basal Pu or inhibit 8CPTcAMP-stimulated Pu. Conclusion. Our results indicate that agmatine inhibits AVP stimulated Pu by a cAMP-dependent mechanism. Imidazoline receptors are probably not involved. The possibility exists of an unknown agmatine-selective receptor modulating urea transport in the rat IMCD.