IN-VIVO REGULATION OF MAP KINASES IN RATUS-NORVEGICUS RENAL PAPILLA BY WATER LOADING AND RESTRICTION

In cultured renal cells, hypertonicity activates multiple mitogen-acti vated protein kinases (MAPKs) and enhances the expression of heat shoc k proteins (HSPs). In rats, 24 h water restriction increased mean urin ary osmolality (U-osm) from 2,179+/-153 mOsm/kg to 2,944+/-294 mOsm/kg (P < 0.001) and was associated with significant (P < 0.05) increases in the papillary activity of c-Jun NH2-terminal protein kinase (JNK) b y 22%, extracellular signal-regulated protein kinase (ERK) by 49%, and p38 MAPK by 15%. Conversely, 24 h of water-loading (U-osm 473+/-33 mO sm/kg) caused suppression of JNK activity by 43% (P < 0.001), ERK by 3 9% (P < 0.05), and p38 MAPK by 26% (P < 0.05). No such modulation was observed in the isotonic cortex, c-Jun phosphorylation was decreased i n papilla from water-loaded rats by 45% versus controls. Expression of Hsp 110, inducible Hsp 70, and Hsp 25 was greater in the hyperosmotic papilla than the isosmotic cortex but was not affected by the animal' s hydration state. In cultured inner medullary collecting duct cells, HSP expression was maximal at 500 mOsm/kg, while activation of JNK con tinued to increase. We conclude that under basal conditions of hydrati on, these HSPs are maximally expressed in the hypertonic inner medulla , while the activation of all three members of the MAPK family approac hes but is not maximal.