Epidermal growth factor (EGF)-stimulated inositol phosphate formation in hepatocytes is abolished by pertussis toxin and phorbol esters
The EGF-stimulated rise in intracellular Ca/sup 2 +/ (Ca/sup 2 +/)/sub i/ and Ca/sup 2 +/-dependent protein phosphorylation events in isolated hepatocytes are blocked by pertussis toxin and phorbol ester pretreatment. The present study characterized the EGF-stimulated formation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P/sub 3/) and inositol 1,3,4-trisphosphate (Ins(1,3,4)P/sub 3/) in hepatocytes using HPLC methodology to separate the InsP/sub 3/ isomers. Both 66 nM EGF and 10 nM angiotensin II (ANG II) caused a rapid increase in the Ins(1,4,5)P/sub 3/ isomer although EGF-stimulated formation was smaller. At a concentration of ANG II (0.1 nM) which gave an equivalent rise in (Ca/sup 2 +/)/sub i/ as 66 nM EGF, the kinetics and magnitude of Ins(1,4,5)P/sub 3/ formation were similar. EGF or ANG II-stimulated formation of the Ins(1,3,4)P/sub 3/ isomer was more gradual and increased beyond the level of Ins(1,4,5)P/sub 3/ after 60 sec. The initial EGF and ANG II-stimulated increase in both InsP/sub 3/ isomers was not affected by removing external Ca/sup 2 +/ with a 10-fold excess of EGTA. Pretreatment of rats with pertussis toxin for 72 hrs blocked the ability of EGF to increase Ins(1,4,5)P/sub 3/ but did not affect the increase due to ANG II. Three main pretreatment of cells with 1 ..mu..g/ml phorbol 12-myristate-13-acetate (PMA) also inhibited the EGF-stimulated Ins(1,4,5)P/sub 3/ formation. PMA slightly attenuated Ins(1,4,5)P/sub 3/ formation stimulated by 0.1 nM ANG II but not enough to affect the Ca/sup 2 +/ signal. These data suggest that the signal transduction system used by EGF receptors to increase Ins (1,4,5)P/sub 3/ in hepatocytes is somehow different from that used by ANG II receptors.
- Research Organization:
- Univ. of Virginia School of Medicine, Charlottesville
- OSTI ID:
- 6065829
- Report Number(s):
- CONF-870644-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 46:6; Conference: 78. annual meeting of the American Society of Biological Chemists conference, Philadelphia, PA, USA, 7 Jun 1987
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
GROWTH FACTORS
BIOCHEMICAL REACTION KINETICS
RECEPTORS
PHORBOL ESTERS
BIOLOGICAL EFFECTS
PHOSPHATES
BIOSYNTHESIS
TOXINS
ANGIOTENSIN
CALCIUM COMPOUNDS
INOSITOL
ISOMERS
LIQUID COLUMN CHROMATOGRAPHY
LIVER CELLS
PHOSPHORYLATION
RATS
ALKALINE EARTH METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
ANTIGENS
CARBOHYDRATES
CARCINOGENS
CARDIOVASCULAR AGENTS
CHEMICAL REACTIONS
CHROMATOGRAPHY
DRUGS
ESTERS
GLOBULINS
INOSITOLS
KINETICS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
MITOGENS
MONOSACCHARIDES
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PHOSPHORUS COMPOUNDS
PROTEINS
REACTION KINETICS
RODENTS
SACCHARIDES
SEPARATION PROCESSES
SOMATIC CELLS
SYNTHESIS
TOXIC MATERIALS
VASOCONSTRICTORS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology