MECHANISMS OF RENAL PROSTAGLANDIN TRANSPORT

Project: Research project

Project Details

Description

Prostaglandins (PGs) and thromboxanes play a fundamental role in renal
physiology. PGs synthesized in the kidney are secreted into the urine by
active uptake into the proximal tubule cell, followed by translocation
across the luminal membrane. The molecular mechanism of renal PG transport
has remained unclear. Our laboratory has identified a cDNA homologue of a
recently-cloned organic anion transporter, which we call "OATP-2", that is
expressed in rat kidney. When expressed in cultured mammalian cells or in
Xenopus oocytes, OATP-2 catalyzes transport of PGE2 equals approximately
PGF2alpha > TxB2>> 6-keto-PGF-1alpha. The Km for PGE2 is approximately 100
nM. Several classic organic anions inhibit OATP-2-mediated PG transport.

Thus, OATP-2 is a novel prostaglandin transporter.

The long term objective of this five-year proposal is to understand, at a
molecular level, the localization, function, structure, and regulation of
OATP-2, especially as these pertain to the kidney. The Specific Aims are
to:

l. Characterize OATP-2 mRNA expression and clone renal isoforms.

2. Immunologically characterize OATP-2 protein expression.

3. Define the fundamental transport properties of cloned rat OATP-2.

4. Initiate structure-function analysis of OATP-2.

5. Examine the regulation of OATP-2 by kinases and steroid hormones.

The proposed experiments are likely to yield fundamental information about
the cellular and molecular mechanisms of PG transport in the kidney and
other tissues, and about organic anion transport in general.
StatusFinished
Effective start/end date5/1/954/30/96

Funding

  • National Institute of Diabetes and Digestive and Kidney Diseases

ASJC

  • Nephrology
  • Physiology
  • Transportation
  • Cell Biology
  • Histology

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