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


CONCLUSIONS
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.
Rouch
Alexander J
AJ
Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma 74107, USA. USA. rouch@osu-com.okstate.edu
Kudo
Lúcia H
LH
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D004837:Epinephrine / Q000494:pharmacology; D054755:Imidazoline Receptors; D066298:In Vitro Techniques; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism; D012076:Renal Agents / Q000494:pharmacology*; D013566:Sympathomimetics / Q000494:pharmacology; D014508:Urea / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D054755:Imidazoline Receptors; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; D012076:Renal Agents; D013566:Sympathomimetics; D001127:Arginine Vasopressin; D015016:Yohimbine; D000376:Agmatine; D014508:Urea; D000242:Cyclic AMP; D004837:Epinephrine