Nerve growth factor regulates HCO3/- absorption in thick ascending limb: Modifying effects of vasopressin

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15 Scopus citations

Abstract

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 HCO3/- absorption by nerve growth factor (NGF) in the rat medullary thick ascending limb (MTAL), which absorbs HCO3/- via apical membrane Na+/H+ exchange. MTAL were perfused in vitro with 25 mM HCO3/- solutions (pH 7.4; 290 mosmol/kgH2O). Addition of 0.7 nM NGF to the bath decreased HCO3/- 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 HCO3/- 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 HCO3/- absorption are distinct. Hypertonicity blocked the inhibition but not the AVP-dependent stimulation, 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/- 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 HCO3/- absorption.

Original languageEnglish (US)
Pages (from-to)C931-C939
JournalAmerican Journal of Physiology - Cell Physiology
Volume274
Issue number4 43-4
DOIs
StatePublished - Apr 1998

Keywords

  • Hypertonicity
  • Protein kinase C
  • Signal transduction
  • Sodium/hydrogen exchange
  • Tyrosine kinases

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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