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The effect of pregnancy and estradiol-17 beta treatment on the biliary transport maximum of dibromosulfophthalein, and the glucuronide conjugates of 5-phenyl-5-p-hydroxyphenyl(/sup 14/C)hydantoin and (/sup 14/C)morphine in the isolated perfused rat liver

Journal Article · · Drug Metab. Dispos.; (United States)
OSTI ID:6853456
;
The biliary transport maximum (Tm) of three organic axions was determined in the isolated perfused livers of untreated female (control), estradiol-17 beta (E2)-treated female (1 mg/kg/day, s.c. for 14 days), and pregnant (19-21 days of gestation) rats. Dibromosulfophthalein (DBSP), 5-phenyl-5-p-hydroxyphenyl(/sup 14/C)hydantoin (HPPH) and (/sup 14/C)morphine were infused continuously into the perfusate for a total dose of 41.2, 18, or 40.5 mumol, respectively. The concentration of (/sup 14/C)HPPH and (/sup 14/C)morphine declined in the perfusate, whereas the concentrations of (/sup 14/C)HPPH glucuronide and (/sup 14/C)morphine glucuronide increased during the 90-min experiment, indicating that the rate of formation of the glucuronide exceeded its rate of excretion in bile. E2 treatment decreased the Tm (nmol/min/g liver) for (/sup 14/C)HPPH glucuronide and (/sup 14/C)morphine glucuronide but not for DBSP, whereas pregnancy decreased the Tm for all three organic anions. Pregnancy, and to a lesser extent E2 treatment, increased liver weight. When expressed per whole liver, the Tm was not altered by pregnancy for any of three organic anions. E2 treatment increased the Tm for DBSP, had no effect on the Tm for HPPH glucuronide and decreased the Tm for (/sup 14/C)morphine glucuronide. These data suggest the presence of multiple carriers for organic anions which are differentially affected by estrogen treatment and pregnancy.
Research Organization:
Department of Pharmacology, College of Medicine, University of Kentucky, Lexington
OSTI ID:
6853456
Journal Information:
Drug Metab. Dispos.; (United States), Journal Name: Drug Metab. Dispos.; (United States) Vol. 10:4; ISSN DMDSA
Country of Publication:
United States
Language:
English

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Related Subjects

551001* -- Physiological Systems-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALDEHYDES
ALKALOIDS
ANALGESICS
ANIMALS
AROMATICS
BILIARY TRACT
BIOLOGICAL EFFECTS
BIOLOGICAL FUNCTIONS
BODY
BROMOSULFOPHTHALEIN
CARBON 14 COMPOUNDS
CARBOXYLIC ACID ESTERS
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CLEARANCE
DIGESTIVE SYSTEM
DRUGS
ESTERS
ESTRADIOL
ESTRANES
ESTROGENS
EXCRETION
FEMALES
FUNCTIONS
GLANDS
GLUCURONIC ACID
HORMONES
HYDROXY ACIDS
HYDROXY COMPOUNDS
INDICATORS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
MAMMALS
MORPHINE
NARCOTICS
OPIUM
ORGANIC ACIDS
ORGANIC BROMINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PERFUSED ORGANS
PHENOLS
POLYPHENOLS
PREGNANCY
RATS
REAGENTS
RODENTS
STEROID HORMONES
STEROIDS
SULFONIC ACIDS
TRACER TECHNIQUES
VERTEBRATES