NERVE GROWTH-FACTOR REGULATES HCO3- ABSORPTION IN THICK ASCENDING LIMB - MODIFYING EFFECTS OF VASOPRESSIN

Growth factors stimulate Na+/H+ exchange activity in many cell types b ut their effects on acid secretion via this mechanism in renal tubules are poorly understood. We examined the regulation of HCO3- absorption by nerve growth factor (NGF) in the rat medullary thick ascending lim b (MTAL), which absorbs HCO3- via apical membrane Na+/H+ exchange. MTA L were perfused in vitro with 25 mM HCO3- solutions (pH 7.4; 290 mosmo l/kgH(2)O). Addition of 0.7 nM NGF to the bath decreased HCO3- absorpt ion from 13.1 +/- 1.1 to 9.6 +/- 0.8 pmol . min(-1) . mm(-1) (P < 0.00 1). In contrast, with 10(-10) M arginine vasopressin (AVP) in the bath , addition of NGF to the bath increased HCO3- absorption from 8.0 +/- 1.6 to 12.5 +/- 1.3 pmol . min(-1) . mm(-1) (P < 0.01). Both effects o f NGF were blocked by genistein, consistent with the involvement of ty rosine kinase pathways. However, the AVP-dependent stimulation require d activation of protein kinase C (PKC), whereas the inhibition was PKC independent, indicating that the NGF-induced signaling pathways leadi ng to inhibition and stimulation of HCO3- absorption are distinct. Hyp ertonicity blocked the inhibition but not the AVP-dependent stimulatio n, suggesting that hypertonicity and NGF may inhibit HCO3- absorption via a common mechanism. These data demonstrate that NGF inhibits HCO3- absorption in the MTAL under basal conditions but stimulates HCO3- ab sorption in the presence of AVP, effects that are mediated through dis tinct signal transduction pathways. They also show that AVP is a criti cal determinant of the response of the MTAL to growth factor stimulati on and suggest that NGF can either inhibit or stimulate apical Na+/Hexchange activity depending on its interactions with other regulatory factors. Locally produced growth factors such as NGF may play a role i n regulating renal tubule HCO3- absorption.