Locally formed dopamine inhibits Na+-K+-ATPase activity in rat renal cortical tubule cells.
Dopamine, generated locally from L-dopa, inhibits Na+-K+-ATPase in permeabilized rat proximal tubules under maximum transport rate conditions for sodium. To determine whether locally formed dopamine inhibits Na+-K+-ATPase activity in intact cortical tubule cells we studied the effect of L-dopa on ouabain-sensitive oxygen consumption rate (QO2) and 86Rb uptake in renal cortical tubule cell suspensions. L-Dopa (10(-4) M) did not affect ouabain-insensitive QO2 or mitochondrial respiration. However, L-dopa inhibited ouabain-sensitive QO2 in a concentration-dependent manner, with half-maximal inhibition (K0.5) of 5 x 10(-7) M and a maximal inhibition of 14.1 +/- 1.5% at 10(-4) M (P less than 0.05). L-Dopa also blunted the nystatin-stimulated QO2 in a concentration-dependent manner, with a K0.5 of 5 x 10(-8) M and a maximal inhibition of 21.8 +/- 1.2% at 10(-5) M (P less than 0.05), indicating that L-dopa directly inhibits Na+-K+-ATPase activity and not sodium entry. Ouabain-sensitive 86Rb uptake was also inhibited by L-dopa (16.0 +/- 2.4%, P less than 0.05). Carbidopa (10(-4) M), an inhibitor of the conversion of L-dopa to dopamine, eliminated the effect of L-dopa on ouabain-sensitive QO2 and 86Rb uptake, indicating that dopamine rather than L-dopa was the active agent. The finding that the L-dopa concentration-response curve was shifted to the left by one order of magnitude in the presence of nystatin suggests that the inhibitory effect is enhanced when the intracellular sodium concentration is increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Seri
I
I
Renal Division, Brigham and Women's Hospital, Boston, Massachusetts.
Kone
B C
BC
Gullans
S R
SR
Aperia
A
A
Brenner
B M
BM
Ballermann
B J
BJ
D000818:Animals; D002230:Carbidopa / Q000494:pharmacology; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004791:Enzyme Inhibitors; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000201:enzymology* / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000201:enzymology* / Q000502:physiology; D007700:Kinetics; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D009761:Nystatin / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012413:Rubidium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D009761:Nystatin; D007980:Levodopa; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium; D002230:Carbidopa; D004298:Dopamine