PKC regulation of organic anion secretion in perfused S2 segments of
rabbit proximal tubules
โปรตีนไคเนสซี (PKC) ในการควบคุมการคัดหลั่งสารอินทรีย์ประจุลบโดยท่อไตของกระต่าย ส่วน S2 proximal ขณะที่ถูก perfused
Apichai Shuprisha, D. of Physiology, F. of Sci., PSU.
Ronald M. Lynch, Assoc. Prof., College of Medicine, U. of Arizona, Tucson, Arizona, USA.
Stephen H. Wright, Prof., College of Medicine, U. of Arizona, Tucson, Arizona, USA.
William H. Dantzler, Prof., College of Medicine, U. of Arizona, Tucson, Arizona, USA.
Corresponding e-mail : sapichai@ratree.psu.ac.th or dantzler@u.arizona.edu
Grant : National Institutes of Health Research, Southwest Environmental Health Science
Center, USA
Published : Am J Physiol Renal Physiol 2000, 278 : F104-F109
Key words : fluorescein, organic anion/dicarboxylate exchanger, transepi-thelialtransport
in real time, bradykinin, phenylephrin, phorbol 12-myristate 13-acetate,
1,2-dioctanoyl-sn-glycerol, staurosporine, bisindolylmaleimide I
To examine the role of protein kinase C (PKC) in organic anion (OA) secretion, we used epi-fluorescence microscopy to study steady-state transepithelial secretion of 1 mM 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 mM 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 se-cretion, suggesting that the basal FL secretion rate was not under influence of PKC. Addition of 1 mM of either the peptide hormone bradykinin (BK) or the a1-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 phy-siological role in regulating OAsecretion via PKC activation.
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