Heterologous regulation of hepatocyte EGF receptors by norepinephrine

Conference · Sat Mar 01 00:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5454383

Cruise, J J; Cotecchia, S; Knechtle, S; Bollinger, R; Michalopoulos, G

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-; TRN: 86-026542
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
• Country of Publication: United States
• Language: English

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