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Mitogenic stimuli and phosphatidylinositol (PI) turnover in cultured 3T3 fibroblasts

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:5389207
;
The hydrolysis of PI and polyphosphoinositides by phopholipase C is an early and rapid response to cell activation by a variety of neurotransmitters, hormones, growth factors and pharmacological agonists. The authors have examined the role of PI turnover and the generation of second messengers (diacylglycerol and inositol trisphosphate) in the mitogenic response of cultured Balb/c and Swiss 3T3 cells to polypeptide growth factors. Cells were prelabelled with /sup 3/H inositol for 18-20 hours, washed and suspended in Herpes + Li/sup +/ buffer, and stimulated with platelet-derived growth factor (PDGF), vasopressin, insulin, and other growth factors. PI turnover was measured as the increase in total inositol phosphate (IP) production. IP1, IP2, and IP3 were characterized by sequential elution from a Dowex column. Partially purified PDGF produced a 2-4 fold stimulation of total IP production. This was seen as early as 30 seconds after stimulation and increased for up to 1-2 hours. Balb/c cells were more sensitive than Swiss cells to the mitogenic and PI effects of PDGF. Other mitogenic stimuli had differential effects on PI turnover. Vasopressin (4-400 ng/ml) markedly stimulated PI turnover (3-6 fold) in Swiss, but not Balb/c cells. Insulin (100 ng/ml - 10 ..mu..g/ml) increased total IP to a greater degree in Balb/c cells. Epidermal growth factor (10 ng/ml - 10 ..mu..g/ml) had no effect on PI turnover and fibroblast growth factor (10 ng/ml - 10 ..mu..g/ml) only stimulated at the higher concentrations in Swiss cells. Thrombin (1U/ml - 10 U/ml) produced a 1.5 - 2 fold stimulation in Balb/c cells. Thus, various polypeptide growth factors have differential effects on PI turnover depending on their mitogenic potential and the effector cell type.
Research Organization:
American Cyanamid Co., Pearl River, NY
OSTI ID:
5389207
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
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL VARIABILITY
CARBOHYDRATES
CARBOXYLESTERASES
CELL CULTURES
CHEMICAL REACTIONS
COAGULANTS
CONNECTIVE TISSUE CELLS
DECOMPOSITION
DRUGS
ENZYMES
ESTERASES
FIBROBLASTS
HEMATOLOGIC AGENTS
HEMOSTATICS
HORMONES
HYDROLASES
HYDROLYSIS
INOSITOL
INOSITOLS
INSULIN
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIPASE
LYSIS
MAMMALS
MICE
MITOGENS
MONOSACCHARIDES
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PEPTIDE HORMONES
PEPTIDE HYDROLASES
PEPTIDES
PHOSPHATES
PHOSPHORUS COMPOUNDS
PITUITARY HORMONES
POLYPEPTIDES
PROTEINS
RODENTS
SACCHARIDES
SERINE PROTEINASES
SOLVOLYSIS
SOMATIC CELLS
THROMBIN
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VASOPRESSIN
VERTEBRATES