TY - JOUR T1 - Dexmedetomidine Inhibits Osmotic Water Permeability in the Rat Cortical Collecting Duct JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 62 LP - 69 VL - 281 IS - 1 AU - Alexander J. Rouch AU - Lúcia H. Kudo AU - Connie Hébert Y1 - 1997/04/01 UR - http://jpet.aspetjournals.org/content/281/1/62.abstract N2 - The purpose of this study was to determine whether the selectivealpha-2 agonist dexmedetomidine inhibits basic transport properties in the rat cortical collecting duct (CCD). Sprague-Dawley rat CCDs were isolated and perfused to allow measurement of osmotic water permeability (Pf), transepithelial voltage (Vt) and resistance (Rt). Arginine vasopressin (AVP) increases Pf, hyperpolarizes Vt and decreases Rt in the CCD via stimulation of adenylyl cyclase. Dexmedetomidine at 100 nM added to the basolateral side of the CCD reduced AVP-stimulated Pf by 95% to 100%, and the alpha-2 antagonist atipamezole reversed the inhibition. In the presence of the protein kinase C inhibitor staurosporine, dexmedetomidine reduced AVP-stimulated Pf by 70% to 75% compared with the complete inhibition without staurosporine. When Pf was increased by the use of the nonhydrolyzable analog of cAMP, 8-chlorophenylthio-cAMP, in lieu of AVP, dexmedetomidine inhibited Pf by ∼35%. This demonstrated alpha-2-mediated inhibition of Pf despite the presence of constant cellular cAMP levels. Dexmedetomidine reversed AVP-induced effects on Vt and Rt, indicating inhibition of Na+ transport. Results confirm an alpha-2-mediated mechanism that reduces Na+ and water transport in the CCD and suggest that a cellular messenger other than cAMP is involved. This messenger could be protein kinase C. The American Society for Pharmacology and Experimental Therapeutics ER -