Competition of organic anions for furosemide and p-aminohippurate secretion in the rabbit
Journal Article
·
· J. Pharmacol. Exp. Ther.; (United States)
OSTI ID:5429199
The excretion of (/sup 14/C)- or (/sup 35/S)furosemide and (/sup 3/H)-p-aminohippurate (PAH) injected within 4 min into the left renal artery of rabbits was measured under brisk mannitol diuresis. The estimated rate of furosemide secretion during the first pass through the left kidney was lower than that of PAH when neither of the two transport processes were saturated: 7.9 and 12.9% of the total amounts injected were secreted per minute, respectively. Different competitive inhibitors were injected i.v. Probenecid (50 mg/kg) inhibited furosemide and PAH secretion by 95 and 80%, respectively. Pyrazinoate at plasma concentrations of 3 to 5 mM had no effect on either anion. Indomethacin (10 mg/kg) depressed furosemide secretion by 24% but had no effect on PAH secretion. PAH at a concentration of 9 to 17 mM in plasma depressed furosemide secretion by only 44 to 66%. Furosemide did not inhibit PAH secretion when infused into the left renal artery at a rate 5000 times higher than PAH. It was concluded that furosemide is secreted partly by the transport system secreting PAH, for which it had only a low affinity, and partly by a transport system for which indomethacin had some affinity. This latter transport system, in turn, differs from that secreting pyrazinoate. The furosemide-induced natriuresis, in both kidneys, was proportional to the urinary excretion rate of furosemide until the fractional excretion of Na+ reached an apparent maximum of 20 to 30%.
- Research Organization:
- Universite de Lausanne, Switzerland
- OSTI ID:
- 5429199
- Journal Information:
- J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 2; ISSN JPETA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
AMINO ACIDS
ANIMALS
ANTIPYRETICS
ARTERIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BLOOD VESSELS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CARDIOVASCULAR SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CLEARANCE
DAYS LIVING RADIOISOTOPES
DIURETICS
DRUGS
EVEN-ODD NUCLEI
EXCRETION
HIPPURIC ACID
IN VITRO
ISOTOPES
KIDNEYS
LABELLED COMPOUNDS
LIGHT NUCLEI
MAMMALS
MEMBRANE TRANSPORT
METABOLISM
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
RABBITS
RADIOISOTOPES
SULFUR 35
SULFUR ISOTOPES
TRITIUM COMPOUNDS
VERTEBRATES
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
AMINO ACIDS
ANIMALS
ANTIPYRETICS
ARTERIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BLOOD VESSELS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CARDIOVASCULAR SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CLEARANCE
DAYS LIVING RADIOISOTOPES
DIURETICS
DRUGS
EVEN-ODD NUCLEI
EXCRETION
HIPPURIC ACID
IN VITRO
ISOTOPES
KIDNEYS
LABELLED COMPOUNDS
LIGHT NUCLEI
MAMMALS
MEMBRANE TRANSPORT
METABOLISM
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
RABBITS
RADIOISOTOPES
SULFUR 35
SULFUR ISOTOPES
TRITIUM COMPOUNDS
VERTEBRATES