Effects of 20-HETE and 19(S)-HETE on rabbit proximal straight tubule volume transport.
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.
Quigley
R
R
Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, 75235-9063, USA. RQUIGL@medmet.swmed.edu
Baum
M
M
Reddy
K M
KM
Griener
J C
JC
Falck
J R
JR
D000577:Amides / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001693:Biological Transport, Active / Q000187:drug effects; D042926:Cytochrome P-450 CYP4A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis / Q000494:pharmacology*; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D010477:Perfusion; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013450:Sulfones / Q000494:pharmacology
D000577:Amides; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D013450:Sulfones; D016718:Arachidonic Acid; C055986:19-hydroxy-5,8,11,14-eicosatetraenoic acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; C117975:DDMS; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A; D000254:Sodium-Potassium-Exchanging ATPase