INDOMETHACIN AND STAUROSPORINE REVERSE-ALPHA(2) INHIBITION OF WATER TRANSPORT IN RAT IMCD

These studies were conducted to determine if the prostaglandin-synthes is inhibitor indomethacin or the protein kinase C (PKC) inhibitor stau rosporine affect the inhibition of osmotic water permeability (P-f) by the alpha-2 (alpha(2)) agonist dexmedetomidine in the rat inner medul lary collecting duct (IMCD). Terminal IMCDs from Wistar rats were perf used and P-f was increased with either 220 pM arginine vasopressin (AV P) or 0.1. mM 8-chlorophenylthio cyclic adenosine monophosphate (8CPTc AMP). All agents were added to the bathing solution. Dexmedetomidine a t 100 nM inhibited both AVP- and 8CPTcAMP-stimulated P-f. When P-f was increased by AVP, indomethacin at 0.1 mM or 5 mu M reversed the dexme detomidine-induced inhibition by 68% and 43%, respectively. When P-f w as increased by 8CPTcAMP, indomethacin at 0.1 mM or 5 mu M reversed in hibition by 83% and 70%, respectively. Indomethacin increased AVP and 8CPTcAMP-stimulated P-f by 20 to 30% and dexmedetomidine inhibited the AVP+ indomethacin-stimulated P-f. Staurosporine at 10 nM yielded simi lar results. Results suggest that PKC and prostaglandins are involved in the alpha(2) mediated mechanism, and staurosporine and indomethacin -sensitive cellular mediators modulate basal P-f.