Background:
Agmatine, a putative endogenous ligand for imidazoline receptors, induces numerous biological effects. the agonist clonidine binds to alpha-2 (alpha2) adrenoceptors and imidazoline receptors, and inhibits arginine vasopressin (avp)-stimulated urea permeability (pu) in the rat inner medullary collecting duct (imcd). dexmedetomidine, a selective alpha2 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 micromol/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 alpha2 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.