Na sup + pump in renal tubular cells is regulated by endogenous Na sup + -K sup + -ATPase inhibitor from hypothalamus

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

OSTI ID:6228234

Cantiello, H F; Chen, E; Ray, S; Haupert, Jr, G T ^[1]

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1. Harvard medical School, Boston, MA (USA)

Bovine hypothalamus contains a high affinity, specific, reversible inhibitor of mammalian Na{sup +}-K{sup +}-ATPase. Kinetic analysis using isolated membrane fractions showed binding and dissociation rates of the hypothalamic factor (HF) to be (like ouabain) relatively long (off rate = 60 min). To determine whether the kinetics of inhibition in intact cells might be more consistent with regulation of physiological processes in vivo, binding and dissociation reactions of HF in intact renal epithelial cells (LLC-PK{sup 1}) were studied using {sup 86}Rb{sup +} uptake and ({sup 3}H)ouabain binding. As with membranes, a 60-min incubation with HF inhibited Na{sup +}-K{sup +}-ATPase in LLC-PK{sub 1} cells. In contrast to membrane studies, no prolonged incubation with LLC-PK{sub 1} was needed to observe inhibition of Na{sup +}-K{sup +}-ATPase. HF caused a 33% inhibition of ouabain-sensitive {sup 86}Rb{sup +} influx within 10 min. Incubation of cells with HF followed by washout showed rapid reversal of pump inhibition and a doubling of pump activity. The dose-response curve for HF inhibition of LLC-PK{sub 1} {sup 86}Rb{sup +} uptake showed a sigmoidal shape consistent with an allosteric binding reaction. Thus HF is a potent regulator of Na{sup +}-K{sup +}-ATPase activity in intact renal cells, with binding and dissociation reactions consistent with relevant physiological processes.

• OSTI ID: 6228234
• 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 COMPOUNDS
ALKALI METAL ISOTOPES
ANIMALS
ATP-ASE
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARBOHYDRATES
CARDIAC GLYCOSIDES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CATIONS
CATTLE
CENTRAL NERVOUS SYSTEM
CHARGED PARTICLES
DAYS LIVING RADIOISOTOPES
DOMESTIC ANIMALS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENZYME INHIBITORS
ENZYMES
GLYCOSIDES
HYDROGEN COMPOUNDS
HYDROLASES
HYPOTHALAMUS
INTERMEDIATE MASS NUCLEI
IONS
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
KIDNEYS
KINETICS
MAMMALS
MEMBRANE TRANSPORT
MINUTES LIVING RADIOISOTOPES
NERVOUS SYSTEM
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
OUABAIN
PHOSPHOHYDROLASES
RADIOISOTOPES
REACTION KINETICS
RUBIDIUM 86
RUBIDIUM ISOTOPES
RUMINANTS
SODIUM COMPOUNDS
STROPHANTHINS
TRITIUM COMPOUNDS
UPTAKE
VERTEBRATES