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Titolo:
Neurotrophin-3 inhibits HCO3- absorption via a cAMP-dependent pathway in renal thick ascending limb
Autore:
Good, DW; George, T;
Indirizzi:
Univ Texas, Med Branch, Dept Med, Galveston, TX 77555 USA Univ Texas Galveston TX USA 77555 anch, Dept Med, Galveston, TX 77555 USA Univ Texas, Med Branch, Dept Physiol & Biophys, Galveston, TX 77555 USA Univ Texas Galveston TX USA 77555 siol & Biophys, Galveston, TX 77555 USA
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
fascicolo: 6, volume: 281, anno: 2001,
pagine: C1804 - C1811
SICI:
0363-6143(200112)281:6<C1804:NIHAVA>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
NERVE GROWTH-FACTOR; MICE LACKING GDNF; CYCLIC ADENOSINE-MONOPHOSPHATE; MEMBRANE NA+/H+ EXCHANGE; PROTEIN-KINASE KINASE; APICAL MEMBRANE; IMMUNOCYTOCHEMICAL LOCALIZATION; BICARBONATE ABSORPTION; SIGNAL-TRANSDUCTION; PERIPHERAL-TISSUES;
Keywords:
neurotrophic factors; kidney; Trk receptors; nerve growth factor; vasopressin;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
59
Recensione:
Indirizzi per estratti:
Indirizzo: Good, DW Univ Texas, Med Branch, Dept Med, 4-200 John Sealy Annex 0562,301Univ Blvd, Galveston, TX 77555 USA Univ Texas 4-200 John Sealy Annex 0562,301 Univ Blvd Galveston TX USA 77555
Citazione:
D.W. Good e T. George, "Neurotrophin-3 inhibits HCO3- absorption via a cAMP-dependent pathway in renal thick ascending limb", AM J P-CELL, 281(6), 2001, pp. C1804-C1811

Abstract

Neurotrophins are expressed in the adult kidney, but their significance isunclear. We showed previously that nerve growth factor (NGF) inhibits HCO3- absorption in the rat medullary thick ascending limb (MTAL) via an extracellular signal-regulated kinase (ERK)-dependent pathway. Here we examined whether other neurotrophic factors affect MTAL HCO3- absorption. Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor had no effect. In contrast, neurotrophin-3 (NT-3, 0.7 nM) inhibited HCO3- absorption by 40% (half-maximal inhibition at similar to0.4 nM). Inhibition by NT-3 was additive to inhibition by NGF. Inhibitors of ERK activation that block inhibition by NGF had no effect on inhibition by NT-3. In contrast, 8-bromo-cAMP or forskolin pretreatment blocked inhibition by NT-3 but not NGF. Inhibition by NT-3 was also blocked by the specific protein kinase A (PKA)inhibitor myristoylated PKI( 14-22) amide and by vasopressin, which inhibits HCO3- absorption via cAMP. Inhibitors of phosphatidylinositol 3-kinase or protein kinase C did not affect NT-3-induced inhibition, but inhibition by NT-3 was eliminated by genistein, consistent with involvement of a receptor tyrosine kinase. These results demonstrate that NT-3 inhibits HCO3- absorption via a cAMP- and PKA-dependent pathway. NT-3 and NGF regulate MTAL ion transport through different signal transduction mechanisms. These studiesestablish a direct role for NT-3 in regulation of renal tubule transport and identify the MTAL as an important target for neurotrophins, which may beinvolved in the control of renal acid excretion.

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Documento generato il 28/01/20 alle ore 14:51:41