Stimulation of na+-k+-2cl- cotransport in rat medullary thick
ascending limb by dopamine.
Aoki, Yuji, Frederick E. Albrecht, Kenneth R. Bergman, and Pedro A.
Jose.
The Second Department of Internal Medicine, Shinshu University
School of Medicine, Matsumoto, Japan, Division of Pediatric
Nephrology, Georgetown University Children's Medical Center, and
Department of Physiology and Biophysics, Georgetown University School
of Medicine, Washington, DC 20007
APStracts 3:0204R, 1996.
Dopamine receptors are present in the medullary thick ascending limb
(mTAL) of Henle but their effect on ion transport in this nephron
segment has not been tested. Therefore, we studied the short-term
effects of dopamine on Na+-K+-2Cl- cotransport (assessed by 100 [mu]M
bumetanide-sensitive 86Rb uptake) in rat mTAL tubular suspensions.
Dopamine (1 [mu]M ) stimulated bumetanide-sensitive 86Rb uptake
(72.1+/-10.6% vs control, n=5) by increasing total 86Rb uptake and by
decreasing bumetanide-insensitive 86Rb
ptake; this effect was concentration-dependent. The dopamine-induced
stimulation of Na+-K+-2Cl- cotransport activity was mimicked by
calyculin A, a protein phosphatase (PP) inhibitor, and Sp-cAMPS, a
protein kinase A (PKA) agonist and blocked by Rp-8-CPT-cAMPS, a PKA
inhibitor (n=5). Dopamine did not increase the stimulatory effect of
the PP inhibitor. However, the stimulatory effect of the PP inhibitor
and PKA agonist was additive and approached the stimulatory effect of
dopamine. The stimulatory effects of dopamine, PP inhibitor and PKA
agonist persisted even when intracellular sodium was clamped by 5
[mu]M monensin. When K+ channels were blocked by 1 mM BaCl2, the
effects of dopamine and calyculin A on the cotransport were no longer
apparent while the stimulatory effect of the PKA agonist was
attenuated. We conclude that dopamine stimulates Na+-K+-2Cl-
cotransport activity. This action is mediated mainly by PKA-dependent
phosphorylation/dephos-phorylation processes and modulated by
dopamine actions on K+ channels.
Received 19 January 1996; accepted in final form 28 May 1996.
APS Manuscript Number R29-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 17 June 96