Autor: |
Quigley R; Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, 75235-9063, USA. RQUIGL@medmet.swmed.edu, Baum M, Reddy KM, Griener JC, Falck JR |
Jazyk: |
angličtina |
Zdroj: |
American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2000 Jun; Vol. 278 (6), pp. F949-53. |
DOI: |
10.1152/ajprenal.2000.278.6.F949 |
Abstrakt: |
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 [(3)H]arachidonic acid and separating the lipid extract by HPLC. There was significant conversion of [(3)H]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 omega- and omega-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. |
Databáze: |
MEDLINE |
Externí odkaz: |
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