Effects of 20-HETE and 19(S)-HETE on rabbit proximal straight tubule volume transport

Raymond P Quigley, Michel G Baum, Komandla Malla Reddy, James C. Griener, J R Falck

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93 Scopus citations


The kidney has the highest abundance of cytochrome P-450 of all extrahepatic organs. Within the kidney, the highest concentration of cytochrome P-450 is found in the proximal tubule. Whether 20- or 19(S)- hydroxyeicosatetraenoic acid (HETE), the major P-450 metabolites of arachidonic acid in the proximal tubule, affect transport in this segment has not been previously investigated. We examined the direct effects of 20- and 19(S)-HETE on volume absorption (J(v)) in the rabbit proximal straight tubule (PST). Production of 20-HETE by rabbit PST was demonstrated by incubating microdissected tubules with [3H]arachidonic acid and separating the lipid extract by HPLC. There was significant conversion of [3H]arachidonic acid to 20-HETE in control tubules that was inhibited by 10-5 M N-methylsulfonyl- 12,12-dibromododec-11-enamide (DDMS). Addition of exogenous 20-HETE had no effect on PST volume transport. However, inhibition of endogenous production of 20-HETE using DDMS stimulated transport. In the presence of DDMS, 20-HETE inhibited PST J(v). 19(S)-HETE in the bathing solution stimulated PST J(v) alone and in the presence of DDMS. Thus ω- and ω-1-hydroxylase products of arachidonic acid have direct effects on PST transport. Endogenous production of 20-HETE may play a role in tonic suppression of transport and may therefore be an endogenous regulator of transport in the proximal tubule.

Original languageEnglish (US)
Pages (from-to)F949-F953
JournalAmerican Journal of Physiology - Renal Physiology
Issue number6 47-6
StatePublished - Jun 2000


  • Cytochrome P-450
  • Hydroxyeicosatetraenoic acids
  • Hypertension
  • In vitro microperfusion
  • Sodium-potassium- adenosinetriphosphatase
  • ω- hydroxylase

ASJC Scopus subject areas

  • Physiology
  • Urology


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