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Am J Physiol Renal Physiol 259: F924-F928, 1990;
0363-6127/90 $5.00
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AJP - Renal Physiology, Vol 259, Issue 6 924-F928, Copyright © 1990 by American Physiological Society

ARTICLES

Inhibition of proximal tubule Na(+)-K(+)-ATPase activity requires simultaneous activation of DA1 and DA2 receptors

A. Bertorello and A. Aperia
Department of Pediatrics, St. Goran's Children's Hospital, Karolinska Institute, Stockholm, Sweden.

This study examines the receptor mechanisms by which dopamine (DA) inhibits Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity in single permeabilized proximal tubule (PCT). Na(+)-K(+)-ATPase activity was inhibited in the presence of both DA1- and DA2-specific agonists but not by either agonist alone. The inhibition induced by DA (10(-6) M) was attenuated in the presence of either of the two DA2-specific antagonists S-sulpiride and YM 09151 at 10(-5) M and in the presence of the DA1 antagonist SCH 23390 (10(-5) M). PCT adenosine 3',5'-cyclic monophosphate (cAMP) levels were significantly increased in the presence of DA and DA1 agonist, but DA2 agonist had no effect on cell cAMP levels. Na(+)-K(+)-ATPase activity was significantly inhibited in PCT incubated with DA2 agonist (10(-5) M) and dibutyryl (DB)-cAMP (10(-6) M) but not with DA2 agonist (10(-5) M) only. PCT Na(+)-K(+)-ATPase activity was also significantly inhibited in the presence of both DA2 agonist (10(-5) M) and forskolin (10(-6) M). Neither DBcAMP (10(-6) M) nor forskolin (10(-6) M) alone inhibited Na(+)-K(+)-ATPase activity. In tubules incubated with DA (10(-8) to 10(-9) M), the presence of DBcAMP (10(-6) M) enhanced the sensitivity by which DA inhibited Na(+)-K(+)-ATPase activity. We conclude that PCT Na(+)-K(+)-ATPase activity is inhibited by a synergistic action of the DA1 and DA2 receptors, with the DA1 receptor acting to increase cell cAMP levels.


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