Locally formed dopamine inhibits Na sup + -K sup + -ATPase activity in rat renal cortical tubule cells

Journal Article · Sat Oct 01 04:00:00 EDT 1988 · American Journal of Physiology; (USA)

OSTI ID:6252710

Seri, I; Kone, B C; Gullans, S R; Aperia, A; Brenner, B M; Ballermann, B J ^[1]

---

1. Harvard Medical School, Boston, MA (USA) Karolinska Institute, Stockholm (Sweden)

Dopamine, generated locally from L-dopa, inhibits Na{sup +}-K{sup +}-ATPase in permeabilized rat proximal tubules under maximum transport rate conditions for sodium. To determine whether locally formed dopamine inhibits Na{sup +}-K{sup +}-ATPase activity in intact cortical tubule cells we studied the effect of L-dopa on ouabain-sensitive oxygen consumption rate ({dot Q}o{sub 2}) and {sup 86}Rb uptake in renal cortical tubule cell suspensions. L-Dopa did not affect ouabain-insensitive {dot Q}o{sub 2} or mitochondrial respiration. However, L-dopa inhibited ouabain-sensitive {dot Q}o{sub 2} in a concentration-dependent manner, with half-maximal inhibition (K{sub 0.5}) of 5 {times} 10{sup {minus}7} M and a maximal inhibition of 14.1 {plus minus} 1.5% at 10{sup {minus}4}M. L-Dopa also blunted the nystatin-stimulated {dot Q}o{sub 2} in a concentration-dependent manner, indicating the L-dopa directly inhibits Na{sup +}-K{sup +}-ATPase activity and not sodium entry. Ouabain-sensitive {sup 86}Rb uptake was also inhibited by L-dopa. Carbidopa, an inhibitor of the conversion of L-dopa to dopamine, eliminated the effect of L-dopa on ouabain-sensitive {dot Q}o{sub 2} and {sup 86}Rb 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. By studying the effect of L-dopa on ouabain-sensitive {dot Q}o{sub 2} at increasing extracellular sodium concentrations in the presence of nystatin, the authors demonstrated that the inhibitory effect of locally formed dopamine on the Na{sup +}-K{sup +}-ATPase is indeed dependent on the sodium available for the enzyme and occurs in an uncompetitive manner.

• OSTI ID: 6252710
• Journal Information: American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 255:4; ISSN 0002-9513; ISSN AJPHA
• Country of Publication: United States
• Language: English

Related Subjects

551001* -- Physiological Systems-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACID ANHYDRASES
ALKALI METAL ISOTOPES
AMINES
ANIMALS
AROMATICS
ATP-ASE
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BODY
CARDIOTONICS
CARDIOVASCULAR AGENTS
DAYS LIVING RADIOISOTOPES
DOPAMINE
DRUGS
ENZYME ACTIVITY
ENZYMES
HYDROLASES
HYDROXY COMPOUNDS
INHIBITION
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
KIDNEYS
KINETICS
MAMMALS
MINUTES LIVING RADIOISOTOPES
NEUROREGULATORS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHENOLS
PHOSPHOHYDROLASES
POLYPHENOLS
RADIOISOTOPES
RATS
REACTION KINETICS
RODENTS
RUBIDIUM 86
RUBIDIUM ISOTOPES
SYMPATHOMIMETICS
TUBULES
UPTAKE
VERTEBRATES