Inhibition of initial transport rate of basolateral organic anion carrier in renal PT by BK and phenylephrine

Michael Gekle, Sigrid Mildenberger, Christoph Sauvant, Dallas Bednarczyk, Stephen H. Wright, William H. Dantzler

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

The effect of ligands for phospholipase C-coupled receptors and of protein kinase C (PKC) stimulation with phorbol ester [phorbol 12-myristate 13-acetate (PMA)] or 1,2-dioctanoyl-sn-glycerol on the activity of the basolateral organic anion transporter (OAT) in S2 segments of single, nonperfused rabbit proximal tubules (PT) was measured with the use of fluorescein and epifluorescence microscopy. The initial uptake rate (25 s, OAT activity) was measured in real time by using conditions similar to those found in vivo. Stimulation of PKC with PMA or 1,2-dioctanoyl-sn-glycerol led to an inhibition of OAT activity, which could be prevented by 10-7 mol/l of the PKC-specific inhibitor bisindolylmaleimide. The α1-receptor agonist phenylephrine as well as the peptide hormone bradykinin induced a reversible decrease of OAT activity, which was prevented by bisindolylmaleimide. The observed effect was not due to a decrease in the concentration of the counterion α-ketoglutarate or to impaired α-ketoglutarate recycling, because it was unchanged in the continuous presence of α-ketoglutarate or methyl succinate. We conclude that physiological stimuli can inhibit the activity of OAT in rabbit PT via PKC. The effect is not mediated by alterations in counterion availability but by a direct action on the OAT.

Original languageEnglish (US)
Pages (from-to)F251-F256
JournalAmerican Journal of Physiology - Renal Physiology
Volume277
Issue number2 46-2
DOIs
StatePublished - Aug 1999

Keywords

  • Bradykinin
  • Isolated proximal tubule
  • Kidney
  • Organic anion transport
  • Protein kinase C

ASJC Scopus subject areas

  • Physiology
  • Urology

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