Effects of 20-HETE and 19(S)-HETE on rabbit proximal straight tubule volume transport
1Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, 75235-9063, USA. RQUIGL@medmet.swmed.edu
Abstract:
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.
Related Concept Videos
Drug Elimination by Renal Route: Tubular Secretion
Renal Tubule and Collecting Duct
Proximal Convoluted Tubule (PCT):
The PCT is the initial segment of the renal tubule, extending from the Bowman's capsule that encloses the glomerulus. Its convoluted structure and microvilli-lined cells increase the surface area for reabsorption. The PCT reabsorbs glucose, amino acids, sodium, and water from the filtrate, ensuring essential...
Reabsorption and Secretion in the Loop of Henle
Renal Drug Excretion: Tubular Reabsorption
Renal Drug Excretion: Tubular Secretion
Physiology of the Genitourinary System II: Tubular Reabsorption and Secretion


