AJP - Renal Physiology, Vol 250, Issue 5 802-F810, Copyright © 1986 by American Physiological Society
Osmolality, vasopressin-stimulated cAMP, and PGE2 synthesis in rat collecting tubule cells
M. Sato and M. J. Dunn
Using rat renal papillary collecting tubule (RPCT) cells in culture, we
examined the interactions of extracellular osmolality,
vasopressin-stimulated cAMP, and prostaglandin E2 (PGE2) synthesis.
Hypertonic solutions composed of equiosmolar amounts of urea and sodium
chloride, 900-2,400 mosM, potentiated the increases of intracellular cAMP
after vasopressin stimulation. Sodium chloride, rather than urea, was the
important solute. The mechanism of this augmented cAMP response was
complex, probably involving increased synthesis, decreased degradation, and
reduced efflux of cAMP from the RPCT cells. The potentiating actions of
hypertonic sodium chloride were specific for vasopressin-stimulated cAMP
and were not observed for forskolin or PGE2-stimulated cAMP. Hypertonic
solutions inhibited RPCT cell PGE2 production, and sodium chloride, rather
than urea, was again the important solute. The enzymatic site of sodium
chloride inhibition of PGE2 synthesis was apparently on the phospholipase
enzymes, assessed by calcium ionophore and bradykinin stimulation, and not
on cyclooxygenase, measured by arachidonic acid responsiveness. Reductions
of osmolality, from 1,800 to 300 mosM, acutely increased PGE2 release,
possibly through a calcium-dependent stimulation of phospholipase. We
conclude that conditions that prevail in vivo during antidiuresis, namely
hypertonicity of the papillary interstitium, may augment vasopressin
responsiveness through increments of collecting tubule cAMP and reductions
of PGE2 which could, in concert, maximize water reabsorption in the
collecting tubule.
