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Heterologous regulation of hepatocyte EGF receptors by norepinephrine

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:5454383
; ; ; ;
Norepinephrine (NE) enhances DNA synthesis in serum-free cultures of adult rat hepatocytes. This effect is mediated via alpha-1 adrenergic receptors and is dependent upon the presence of epidermal growth factor (EGF). Recent work has focused on the ability of NE to enhance EGF-stimulated DNA synthesis by altering cell responsiveness at the level of surface EGF receptors. After 1 hr of preincubation with 10 /sup -5/M NE, specific /sup 125/I-EGF binding was maximally reduced (by approximately 40%). NE reduction of EGF binding, like the stimulation of DNA synthesis, was dose-dependent and became significant at NE concentrations > 10/sup -7/M. NE reduction of EGF binding was also mediated by alpha-1 receptors, as demonstrated by selective inhibition of this effect by prazosin, but not by yohimbine or pindolol. Competition binding curves indicated identical EGF receptor binding affinities in control and NE-treated cultures (Kdapprox. 0.7nM), and saturation binding curves demonstrated that NE had reduced EGF receptor number by 40%. Scatchard analysis estimated the number of binding sites to be 100,000/cell in controls and 60,000/cell in NE-treated groups. Preliminary data indicate that NE, acting via alpha-1 receptors, may be important in the initiation of DNA synthesis during liver regeneration in vivo. Rats subjected to prior hepatic denervation or treated with a specific alpha-1 antagonist showed marked suppression of DNA synthesis 24 hrs after partial hepatectomy.
Research Organization:
Duke Univ. Medical Center, Durham, NC
OSTI ID:
5454383
Report Number(s):
CONF-8604222-
Conference Information:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
AFFINITY
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CULTURES
DAYS LIVING RADIOISOTOPES
DNA REPLICATION
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HORMONES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
KINETICS
LIVER CELLS
MAMMALS
MEMBRANE PROTEINS
NEUROREGULATORS
NORADRENALINE
NUCLEI
NUCLEIC ACID REPLICATION
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PROTEINS
RADIOISOTOPES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SOMATIC CELLS
STEROID HORMONES
SYMPATHOMIMETICS
VERTEBRATES