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
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), Vol. 10:4
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BILIARY TRACT
BIOLOGICAL FUNCTIONS
BROMOSULFOPHTHALEIN
EXCRETION
ESTRADIOL
BIOLOGICAL EFFECTS
MORPHINE
PREGNANCY
CARBON 14 COMPOUNDS
ESTERS
FEMALES
GLUCURONIC ACID
LIVER
PERFUSED ORGANS
RATS
TRACER TECHNIQUES
ALDEHYDES
ALKALOIDS
ANALGESICS
ANIMALS
AROMATICS
BODY
CARBOXYLIC ACID ESTERS
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CLEARANCE
DIGESTIVE SYSTEM
DRUGS
ESTRANES
ESTROGENS
FUNCTIONS
GLANDS
HORMONES
HYDROXY ACIDS
HYDROXY COMPOUNDS
INDICATORS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NARCOTICS
OPIUM
ORGANIC ACIDS
ORGANIC BROMINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
REAGENTS
RODENTS
STEROID HORMONES
STEROIDS
SULFONIC ACIDS
VERTEBRATES
551001* - Physiological Systems- Tracer Techniques