PKC regulation of organic anion secretion in perfused S2 segments of rabbit proximal tubules

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Abstract

To examine the role of protein kinase C (PKC) in organic anion (OA) secretion, we used epifluorescence microscopy to study steady-state transepithelial secretion of 1 μM fluorescein (FL) by isolated perfused S2 segments of rabbit renal proximal tubules. Addition of 100 nM phorbol 12- myristate 13-acetate (PMA), a known PKC activator, to the bathing medium decreased steady-state secretion of FL by ~30% after 25 min. This inhibition was irreversible and, indeed, increased to ~40% at 25 min following removal of PMA [10 μM 1,2-dioctanoyl-sn-glycerol (DOG) produced a comparable inhibition]. The inhibition produced by PMA was blocked when 100 nM of either staurosporine (ST) or bisindolylmaleimide I (BIM), both known PKC inhibitors, was added to the bath for a 20-min preexposure followed by the addition of PMA. ST or BIM alone had no significant effect on FL secretion, suggesting that the basal FL secretion rate was not under influence of PKC. Addition of 1 μM of either the peptide hormone bradykinin (BK) or the α1-receptor agonist phenylephrine (PE), both of which stimulate PKC via a ligand- receptor-PKC coupling reaction, to the bath also inhibited FL secretion by ~22 and ~27%, respectively. However, the inhibition was completely reversible after removal of BK or PE. Pretreatment of tubules with 100 nM BIM eliminated the inhibition of FL secretion produced by exposure to PE. We conclude that PKC negatively regulates the net secretion of OAs in rabbit renal proximal tubules. The data indicate that BK or catecholamines can play a physiological role in regulating OA secretion via PKC activation.

Original languageEnglish (US)
Pages (from-to)F104-F109
JournalAmerican Journal of Physiology - Renal Physiology
Volume278
Issue number1 47-1
DOIs
StatePublished - Jan 2000

Keywords

  • 1,2-dioctanoyl-sn-glycerol
  • Bisindolylmaleimide I
  • Bradykinin
  • Fluorescein
  • Organic anion/dicarboxylate exchanger
  • Phenylephrine
  • Phorbol 12-myristate 13- acetate
  • Staurosporine
  • Transepithelial transport in real time

ASJC Scopus subject areas

  • Physiology
  • Urology

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