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

Citation
M. Gekle et al., Inhibition of initial transport rate of basolateral organic anion carrier in renal PT by BK and phenylephrine, AM J P-REN, 46(2), 1999, pp. F251-F256
Citations number
19
Language
INGLESE
art.tipo
Article
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
ISSN journal
0363-6127 → ACNP
Volume
46
Issue
2
Year of publication
1999
Pages
F251 - F256
Database
ISI
SICI code
0363-6127(199908)46:2<F251:IOITRO>2.0.ZU;2-A
Abstract
The effect of ligands for phospholipase C-coupled receptors and of protein kinase C (PKC) stimulation with phorbol eater [phorbol 12-myristate 13-acet ate (PMA)] or 1,2-dioctanoyl-sn-glycerol on the activity of the basolateral organic anion transporter (OAT) in S2 segments of single, nonperfused rabb it proximal tubules (PT) was measured with the use of fluorescein and epifl uorescence microscopy. The initial uptake rate (25 s, OAT activity) was mea sured in real time by using conditions similar to those found in vivo. Stim ulation 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-specif ic inhibitor bisindolylmaleimide. The alpha(1)-receptor agonist phenylephri ne as well as the peptide hormone bradykinin induced a reversible decrease of OAT activity, which was prevented by bisindolylmaleimide. The observed e ffect was not due to a decrease in the concentration of the counterion alph a-ketoglutarate or to impaired alpha-ketoglutarate recycling, because it wa s unchanged in the continuous presence of alpha-ketoglutarate or methyl suc cinate. We conclude that physiological stimuli can inhibit the activity of OAT in rabbit PT via PKC. The effect is not mediated by alterations in coun terion availability but by a direct action on the OAT.