Studies with doxazosin on the saturable binding of /sup 125/I-LDL by liver in normocholesterolemic mice

Journal Article · Thu Jan 01 04:00:00 EST 1987 · J. Cardiovasc. Pharmacol.; (United States)

DOI:https://doi.org/10.1097/00005344-198706109-00008· OSTI ID:5411943

Nanjee, M N; Miller, N E

Tissue culture studies have provided evidence that alpha 1-adrenergic receptor inhibition with doxazosin increases the number of low-density lipoprotein (LDL) receptors in human fibroblasts. A similar effect occurring in vivo might explain the reduction of plasma LDL concentration observed in some clinical trials of prazosin. In order to examine this question further, mice were given doxazosin 100 or 400 micrograms/kg/day by i.p. injection for 4 days, after which they were killed, blood was collected and livers were excised. Binding of /sup 125/I-labelled human LDL to tissue homogenates, over the concentration range 30-120 micrograms LDL protein/ml, was measured at 37 degrees C in the absence and presence of excess unlabelled LDL. Woolf plots of the results for saturable binding were found to be compatible with a single class of binding site. In control animals Bmax for this receptor was 867 +/- 117 ng LDL protein/mg tissue protein, and the equilibrium dissociation constant was 32.7 +/- 6.6 micrograms LDL protein/ml (mean +/- SD, n = 5). Doxazosin treatment had no effect on either parameter of /sup 125/I-LDL binding. A trend towards a decrease in liver triglyceride concentration with increasing doses of doxazosin was recorded, but there was no evidence for effects on liver cholesterol or serum lipid concentrations.

• Research Organization: United Medical School of Guy's Hospital, London, England
• OSTI ID: 5411943
• Journal Information: J. Cardiovasc. Pharmacol.; (United States), Journal Name: J. Cardiovasc. Pharmacol.; (United States); ISSN JCPCD
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ANTIHYPERTENSIVE AGENTS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BODY
CARDIOVASCULAR AGENTS
CHOLESTEROL
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ESTERS
GLANDS
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIPIDS
LIPOPROTEINS
LIVER
MAMMALS
MEMBRANE PROTEINS
MICE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RODENTS
STEROIDS
STEROLS
TRACER TECHNIQUES
TRIGLYCERIDES
VERTEBRATES