Dopamine inhibits vasopressin-dependent camp production in the rat
cortical collecting duct.
Li, Li, and James A. Schafer, Mary L. Watkins.
Departments of Physiology and Biophysics, Nephrology Research and
Training Center, University of Alabama at Birmingham, Birmingham, AL
35294
APStracts 5:0067F, 1998.
Dopamine inhibits Na+ and water reabsorption in the rat cortical
collecting duct (CCD) in the presence of arginine vasopressin (AVP).
This inhibition appears to involve a D4 dopamine receptor isoform,
which inhibits cAMP production; however, the D1A receptor, which
stimulates cAMP production, is also expressed in the CCD. To
discriminate between these opposing effects, we measured cAMP
production in intact CCD segments. The basal rate of cAMP production
ranged from 6.5 to 10 fmol/mm (of tubule length) over a 7 min
incubation period, and it was unaffected by either dopamine or the
D1A-specific agonist fenoldopam. AVP increased cAMP production to the
range 85 to 153 fmol mm-1 7 min-1. Whereas neither 0.1 nor 1.0 [mu]M
fenoldopam affected AVP-dependent cAMP production, dopamine reduced
it in a dose-dependent manner, achieving a maximum inhibition of 50%
at 10 [mu]M. This effect was reversed by the D4 receptor antagonist
clozapine, but not by pimozide or spiperone (antagonists of D2 and D3
receptors), nor by calphostin C or chelerythrine (inhibitors of
protein kinase C). We conclude that dopamine inhibits transepithelial
Na+ transport and osmotic water permeability in the presence of AVP
by inhibition of cAMP production, which is mediated by the D4
receptor isoform linked via the inhibitory G-protein Gi.
Received 7 July 1997; accepted in final form 5 March 1998.
APS Manuscript Number F218-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 6 April 1998