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

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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)
JournalAmerican Journal of Physiology - Cell Physiology
Volume274
Issue number4 43-4
StatePublished - Apr 1998

Fingerprint

Nerve Growth Factor
Vasopressins
Extremities
Arginine Vasopressin
Baths
Intercellular Signaling Peptides and Proteins
Protein Kinase C
Kidney
Signal transduction
Genistein
Protein-Tyrosine Kinases
Rats
Signal Transduction
Chemical activation
Membranes
Acids

Keywords

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

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

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title = "Nerve growth factor regulates HCO3/- absorption in thick ascending limb: Modifying effects of vasopressin",
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.",
keywords = "Hypertonicity, Protein kinase C, Signal transduction, Sodium/hydrogen exchange, Tyrosine kinases",
author = "David Good",
year = "1998",
month = "4",
language = "English (US)",
volume = "274",
journal = "American Journal of Physiology - Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "4 43-4",

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T1 - Nerve growth factor regulates HCO3/- absorption in thick ascending limb

T2 - Modifying effects of vasopressin

AU - Good, David

PY - 1998/4

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N2 - 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.

AB - 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.

KW - Hypertonicity

KW - Protein kinase C

KW - Signal transduction

KW - Sodium/hydrogen exchange

KW - Tyrosine kinases

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