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Departments of Physiology and Biophysics, Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, Alabama 35294
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 the 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 of 85-153
fmol · mm
1 · 7 min1. Whereas neither 0.1 nor 1.0 µM fenoldopam affected AVP-dependent cAMP production,
dopamine reduced it in a dose-dependent manner, achieving a maximum
inhibition of 50% at 10 µM. This effect was reversed by the
D4 receptor antagonist clozapine
but not by pimozide or spiperone (antagonists of
D2 and
D3 receptors) or 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.
dopamine receptors; arginine vasopressin; antidiuretic hormone; sodium reabsorption; water reabsorption; protein kinase C
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