Regulation of hco absorption by prostaglandin e2 and g proteins in
rat medullary thick ascending limb.
Good, David W., and Thampi George.
Departments of Medicine and Physiology & Biophysics, University
of Texas Medical Branch, Galveston, Texas 77555
APStracts 2:0219F, 1995.
Arginine vasopressin (AVP) inhibits HCO absorption (JHCO3) in the
medullary thick ascending limb (MTAL) of the rat by increasing cyclic
AMP. Hyperosmolality also inhibits JHCO3 via a pathway additive to
inhibition by AVP. To determine whether these regulatory effects are
modulated by prostaglandin E2 (PGE2), MTAL were isolated and perfused
in vitro with 25 mM HCO solutions (pH = 7.4; 290 mosmol/kg H2O). PGE2
(10-6 M in the bath) had no effect on JHCO3 in the absence of AVP. In
contrast, with 10-10 M AVP in the bath solution, addition of 10-8 or
10-6 M PGE2 to the bath increased JHCO3 from 9.7 +/- 0.8 to 14.3 +/-
1.1 pmol/min/mm (P < 0.001). In the presence of both AVP and
hyperosmolaltiy (75 mM NaCl added to perfusate and bath), PGE2
increased JHCO3 from 1.4 +/- 0.1 to 7.5 +/- 0.5 pmol/min/mm (P <
0.005). PGE2 also stimulated JHCO3 in the presence of AVP and
hypertonic urea. Cholera toxin (CTX, 10-12 to 10-9 M in the bath)
inhibited JHCO3 by 40% and this inhibition was reversed by PGE2. PGE2
did not reverse inhibition of JHCO3 by forskolin. The stimulation of
JHCO3 by PGE2 in the presence of AVP was blocked by pretreatment with
pertussis toxin (PTX, 2 x 10-11 or 10-8M). Neither CTX nor PTX
affected inhibition of JHCO3 by hyperosmolality. These results
demonstrate that PGE2 reverses inhibition of JHCO3 by AVP by acting
via a PTX-sensitive G protein (presumably Gi) to inhibit AVP
-stimulated cyclic AMP production. PGE2 may act as a counterregulatory
factor to maintain a stable rate of HCO absorption in the MTAL during
antidiuresis when circulating AVP levels and medullary osmolality are
elevated.
Received 5 July 1995; accepted in final form 18 October 1995.
APS Manuscript Number F212-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95