Oxytocin as an antidiuretic hormone: i. concentration dependence of
action.
Chou, Chung-Lin, Susan R. Digiovanni, Raymond Mejia, Soren Nielsen,
and Mark A. Knepper.
Laboratory of Kidney and Electrolyte Metabolism, National Heart,
Lung and Blood Institute, National Institutes of Health, Bethesda, MD
20892 and Department of Cell Biology, University of Aarhus, DK-8000
Aarhus C, Denmark,
APStracts 2:0034F, 1995.
Circulating concentrations of oxytocin increase to 10-40 pM in rats in
response to osmotic stimuli, suggesting that oxytocin could play a
role in regulation of water balance. The present studies tested
whether oxytocin at such concentrations increases osmotic water
permeability (Pf) in isolated perfused terminal inner medullary
collecting ducts (IMCD). In IMCD segments from Sprague-Dawley rats,
20 pM oxytocin added to the peritubular bath caused a 2-3 fold
increase in Pf, while 200 pM oxytocin increased Pf by 5-6 fold (n=8,
P<0.01). IMCD from Brattleboro rats, which manifest central
diabetes insipidus, exhibited a 2.8-fold increase in Pf in response
to 20 pM oxytocin and a 4.7-fold increase in response to 200 pM
oxytocin. However, in Brattleboro rats, the response to 20 pM
oxytocin was dependent on prior water-restriction of the rats.
Immunoblotting showed no change in the expression of the aquaporin-CD
water channel in Brattleboro rats in response to water restriction.
Nevertheless, immunofluorescence studies of inner medullary tissue
from Brattleboro rats revealed a marked redistribution of the
aquaporin-CD water channels to a predominantly apical and subapical
localization in IMCD cells in response to water restriction, similar
to the redistribution seen in response to vasopressin. Mathematical
modelling studies revealed that the measured increase in Pf in
response to oxytocin is sufficient to generate a concentrated urine.
We conclude that oxytocin can function physiologically as an
antidiuretic hormone, mimicking the short-term action of vasopressin
on water permeability, albeit with somewhat lower potency.
Received 20 December 1994; accepted in final form 20 February
1995.
APS Manuscript Number F451-4.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 21 March 1995.