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Am J Physiol Cell Physiol 274: C931-C939, 1998;
0363-6143/98 $5.00
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Vol. 274, Issue 4, C931-C939, April 1998

Nerve growth factor regulates HCOminus 3 absorption in thick ascending limb: modifying effects of vasopressin

David W. Good
(With the Technical Assistance of Thampi George)

Departments of Medicine and of Physiology and Biophysics, University of Texas Medical Branch, Galveston, Texas 77555

Growth factors stimulate Na+/H+ 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 HCO-3 absorption by nerve growth factor (NGF) in the rat medullary thick ascending limb (MTAL), which absorbs HCO-3 via apical membrane Na+/H+ exchange. MTAL were perfused in vitro with 25 mM HCO-3 solutions (pH 7.4; 290 mosmol/kgH2O). Addition of 0.7 nM NGF to the bath decreased HCO-3 absorption from 13.1 ± 1.1 to 9.6 ± 0.8 pmol · min-1 · mm-1 (P < 0.001). In contrast, with 10-10 M arginine vasopressin (AVP) in the bath, addition of NGF to the bath increased HCO-3 absorption from 8.0 ± 1.6 to 12.5 ± 1.3 pmol · min-1 · mm-1 (P < 0.01). Both effects of NGF were blocked by genistein, consistent with the involvement of tyrosine kinase pathways. However, the AVP-dependent 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 HCO-3 absorption are distinct. Hypertonicity blocked the inhibition but not the AVP-dependent stimulation, suggesting that hypertonicity and NGF may inhibit HCO-3 absorption via a common mechanism. These data demonstrate that NGF inhibits HCO-3 absorption in the MTAL under basal conditions but stimulates HCO-3 absorption in the presence of AVP, effects that are mediated through distinct signal transduction pathways. They also show that AVP is a critical determinant of the response of the MTAL to growth factor stimulation and suggest that NGF can either inhibit or stimulate apical Na+/H+ exchange activity depending on its interactions with other regulatory factors. Locally produced growth factors such as NGF may play a role in regulating renal tubule HCO-3 absorption.

sodium/hydrogen exchange; protein kinase C; signal transduction; hypertonicity; tyrosine kinases


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