Distribution of binding sites for thromboxane a2 in the mouse
kidney.
Mannon, Roslyn B., Thomas M. Coffman, and Peter J. Mannon.
Divisions of Nephrology and Gastroenterology, Department of
Medicine, Duke University and Durham VA Medical Centers, Durham, NC
27705
APStracts 3:0147F, 1996.
Thromboxane A2 (TXA2) is a potent vasoconstrictor eicosanoid that has
been implicated in the pathogenesis of both human and experimental
renal diseases. The biologic actions of TXA2 in the kidney are
mediated through specific cell-surface receptors. In this report, we
characterize the distribution of thromboxane receptors (TXR) within
the normal mouse kidney by receptor autoradiography. Using the
iodinated TXR agonist [125I]BOP, TXA2 binding sites were detected
throughout the kidney. Competitive inhibition curves of whole kidney
binding demonstrated an IC50 of 6.5 nM. When Scatchard analysis was
performed on anatomically discrete regions, the [125I]BOP binding in
the medulla was best fit by a one-site model with a Kd of 8.2 +/- 2.2
nM. In contrast, [125I]BOP binding in the cortex was better described
by a two-site model, with estimated of Kd = 262 +/- 16 pM for a
higher affinity site, and 16.9 +/- 1.3 nM for a lower affinity site.
These sites do not appear to represent receptor isoforms that arise
from alternative splicing of mRNA. The lower affinity binding sites
may represent a novel TXR or an alternative affinity state for the
previously characterized high affinity binding site.
Received 18 October 1995; accepted in final form 15 August 1996.
APS Manuscript Number F355-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996