Luminal prostaglandin e receptors regulate salt and water transport
in rabbit cortical collecting duct.
Sakairi, Yasunori, Harry R. Jacobson, Thomas D. Noland, and Matthew D.
Breyer.
Departments of Medicine, Division of Nephrology, Vanderbilt
University, Nashville, TN 37232
APStracts 2:0059F, 1995.
PGE2 is the major renal cyclooxygenase metabolite of arachidonic acid.
Urinary excretion of PGE2 is increased by dietary salt restriction as
well in cirrhosis and congestive heart failure. To determine whether
urinary PGE2 affects transport along the nephron, the actions of
luminal PGE2 were studied in the isolated perfused rabbit CCD.
Luminal PGE2 transiently hyperpolarized transepithelial voltage (Vt)
in a dose dependent manner (half maximal effect 10-8M) in contrast to
a sustained depolarization of Vt produced by basolateral PGE2.
Luminal PGE2 (0.1[mu]M) also significantly stimulated osmotic water
permeability in the CCD. In CCDs cultured on semipermeable supports,
apical PGE2 stimulated cAMP production, suggesting the effects of
luminal PGE2 are mediated by adenylyl cyclase-stimulating EP2 or EP4
receptors. Sulprostone, a PGE2 analog selective for EP1 and EP3
receptors, affected Vt only when applied from the basolateral but not
the luminal surface. Luminal application of the EP2 receptor agonist,
butaprost was also without effect. These results suggests that
luminal PGE2 affects Vt via a butaprost-insensitive EP4 receptor. The
Vt effect of luminal PGE2 was not blocked by pertussis toxin also
arguing against an EP3 mediated Gi-coupled effect. Finally 1 [mu]M
luminal PGE2 only slightly increased CCD [Ca2+]i, in contrast to the
marked increase in [Ca2+]i produced by basolateral PGE2 (0.1[mu]M).
These results suggest luminal EP4 receptors stimulate cAMP generation
in the CCD, thereby affecting water and ion transport. Urinary PGE2
may importantly regulate salt and water transport in the collecting
duct.
Received 23 August 1994; accepted in final form 28 March 1995.
APS Manuscript Number F301-4.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 April 1995.