Nerve growth factor regulates HCO3 2 absorption in thick ascending limb: modifying effects of vasopressin

absorption in thick ascending limb: modifying effects of vasopressin. Am. J. Physiol. 274 (Cell Physiol. 43): C931– C939, 1998.—Growth factors stimulate Na1/H1 exchange activity in many cell types but their effects on acid secretion via this mechanism in renal tubules are poorly understood. We examined the regulation of HCO3 2 absorption by nerve growth factor (NGF) in the rat medullary thick ascending limb (MTAL), which absorbs HCO3 2 via apical membrane Na1/H1 exchange. MTAL were perfused in vitro with 25 mM HCO3 2 solutions (pH 7.4; 290 mosmol/kgH2O). Addition of 0.7 nM NGF to the bath decreased HCO3 2 absorption from 13.1 6 1.1 to 9.6 6 0.8 pmol ·min21 ·mm21 (P , 0.001). In contrast, with 10210 M arginine vasopressin (AVP) in the bath, addition of NGF to the bath increased HCO3 2 absorption from 8.0 6 1.6 to 12.5 6 1.3 pmol ·min21 ·mm21 (P , 0.01). Both effects of NGF were blocked by genistein, consistent with the involvement of tyrosine kinase pathways. However, the AVPdependent stimulation required activation of protein kinase C (PKC), whereas the inhibition was PKC independent, indicating that the NGF-induced signaling pathways leading to inhibition and stimulation of HCO3 2 absorption are distinct. Hypertonicity blocked the inhibition but not the AVPdependent stimulation, suggesting that hypertonicity and NGF may inhibit HCO3 2 absorption via a common mechanism. These data demonstrate that NGF inhibits HCO3 2