Abstract: | Growth factorsstimulateNa+/H+exchange activity in many cell types but their effects on acidsecretion via this mechanism in renal tubules are poorly understood. Weexamined the regulation of HCO3absorption by nerve growth factor (NGF) in the rat medullary thickascending limb (MTAL), which absorbs HCO3via apical membraneNa+/H+exchange. MTAL were perfused in vitro with 25 mMHCO3 solutions (pH 7.4; 290 mosmol/kgH2O). Addition of 0.7 nMNGF to the bath decreased HCO3absorption from 13.1 ± 1.1 to 9.6 ± 0.8 pmol · min1 · mm1(P < 0.001). In contrast, with1010 M arginine vasopressin(AVP) in the bath, addition of NGF to the bath increasedHCO3 absorption from 8.0 ± 1.6 to12.5 ± 1.3 pmol · min1 · mm1(P < 0.01). Both effects of NGF wereblocked by genistein, consistent with the involvement of tyrosinekinase pathways. However, the AVP-dependent stimulation requiredactivation of protein kinase C (PKC), whereas the inhibition was PKCindependent, indicating that the NGF-induced signaling pathways leadingto inhibition and stimulation of HCO3absorption are distinct. Hypertonicity blocked the inhibition but notthe AVP-dependent stimulation, suggesting that hypertonicity and NGFmay inhibit HCO3 absorption via acommon mechanism. These data demonstrate that NGF inhibitsHCO3 absorption in the MTAL underbasal conditions but stimulates HCO3 absorption in the presence of AVP, effects that are mediated through distinct signal transduction pathways. They also show that AVP is acritical determinant of the response of the MTAL to growth factorstimulation and suggest that NGF can either inhibit or stimulateapical Na+/H+ exchange activitydepending on its interactions with other regulatory factors. Locallyproduced growth factors such as NGF may play a role in regulating renaltubule HCO3 absorption. |