DEXMEDETOMIDINE INHIBITS OSMOTIC WATER PERMEABILITY IN THE RAT CORTICAL COLLECTING DUCT

The purpose of this study was to determine whether the selective alpha -2 agonist dexmedetomidine inhibits basic transport properties in the rat cortical collecting duct (CCD). Sprague-Dawley rat CCDs were isola ted and perfused to allow measurement of osmotic water permeability (P -f), transepithelial voltage (V-t) and resistance (R-t). Arginine vaso pressin (AVP) increases P-f, hyperpolarizes V-t and decreases R-t in t he CCD via stimulation of adenylyl cyclase. Dexmedetomidine at 100 nM added to the basolateral side of the CCD reduced AVP-stimulated P-f by 95% to 100%, and the alpha-2 antagonist atipamezole reversed the inhi bition. In the presence of the protein kinase C inhibitor staurosporin e, dexmedetomidine reduced AVP-stimulated P-f by 70% to 75% compared w ith the complete inhibition without staurosporine. When P-f was increa sed by the use of the nonhydrolyzable analog of cAMP, 8-chlorophenylth io-cAMP, in lieu of AVP, dexmedetomidine inhibited P-f by similar to 3 5%. This demonstrated alpha-2-mediated inhibition of P-f despite the p resence of constant cellular cAMP levels. Dexmedetomidine reversed AVP -induced effects on V-t and R-t, indicating inhibition of Na+ transpor t. 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.