P450 arachidonate metabolites mediate bradykinin-dependent inhibition of NaCl transport in the rat thick ascending limb

Jay S. Grider, Jeff C. Falcone, Eric L. Kilpatrick, Cobern E. Ott, Brian A. Jackson

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Recent studies from this laboratory demonstrated that bradykinin transiently elevates intracellular Ca2+ and inhibits Cl- reabsorption in the in vitro microperfused medullary thick ascending limb (mTAL) of the rat. The present study was designed to identify the intracellular signaling mechanism(s) that mediate this response. Preincubation with the intracellular calcium chelator BAPTA (10-5 M) completely eliminated the bradykinin-dependent increase in intracellular Ca2+ and the suppression of Cl- transport. Preincubation with the cGMP-dependent protein kinase inhibitor H-89 (10-5 M) had no effect on the transport response to bradykinin. In contrast, 17-octadecynoic acid (17-ODYA; 10-5 M), a suicide-substrate inhibitor of renal cytochrome P450 ω-hydroxylase, completely blocked the transport response to bradykinin, while the cyclooxygenase inhibitor sodium meclofenamate (10-5 M) had no effect. Finally, addition of the cytochrome P450 ω-hydroxylase metabolite 20-hydroxyeicosatetraenoic acid (20-HETE; 10-8 M) to the bathing medium significantly inhibited Cl- transport in the mTAL (Δ -39 ± 6.0%; p < 0.05), while the epoxygenase metabolite 5,6-epoxyeicosatrienoic acid (5,6-EET; 10-8 M) had no effect. These data suggest that the bradykinin-dependent inhibition of Cl- transport in the mTAL of the rat is mediated by cytochrome P450 dependent metabolite(s) of arachidonic acid.

Original languageEnglish
Pages (from-to)91-96
Number of pages6
JournalCanadian Journal of Physiology and Pharmacology
Volume75
Issue number2
DOIs
StatePublished - 1997

Keywords

  • Chloride transport
  • In vitro microperfusion
  • Intracellular Ca
  • Loop of Henle
  • ω-hydroxylase metabolites

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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