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Title: Epidermal growth factor (EGF) stimulated Ca/sup 2 +/ mobilization in hepatocytes is abolished by phorbol esters, pertussis toxin and partial hepatectomy

EGF has been demonstrated to increase free intracellular Ca/sup 2 +/ levels in isolated hepatocytes putatively by generation of the second messenger inositol trisphosphate (IP/sub 3/). Pretreatment of cells with phorbol 12-myristate 13-acetate (PMA) inhibited the EGF (66 nM) stimulated Ca/sup 2 +/ response as measured by quin2. Inhibition by PMA was maximal within 3 min and was concentration dependent (IC/sub 50/ = 13.5 nM). Four other active phorbol ester analogues blocked the Ca/sup 2 +/ response while inactive analogues did not. EGF was unable to increase intracellular Ca/sup 2 +/ levels in hepatocytes isolated from rats treated with pertussis toxin for 72 hrs. Neither PMA nor toxin pretreatment was able to inhibit the Ca/sup 2 +/ response to angiotensin II (Ang II). In hepatocytes isolated 24 hrs after partial hepatectomy, the Ca/sup 2 +/ response to EGF (as measured by phosphorylase activity, EC/sub 50/ = 5 nM) was completely abolished and remained attenuated for 7 days post-hepatectomy. The Ca/sup 2 +/ response to Ang II in this model system was also blunted but required 3 days for development of the full effect and within 7 days full activity is nearly restored. The results suggest that fundamental differences exist inmore » the transduction mechanisms used by these two Ca/sup 2 +/-linked hormones to mobilize intracellular Ca/sup 2 +/ (and putatively increase IP/sub 3/ formation).« less
Authors:
;
Publication Date:
OSTI Identifier:
6984904
Report Number(s):
CONF-8606151-
Journal ID: CODEN: FEPRA
Resource Type:
Conference
Resource Relation:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States); Journal Volume: 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
Research Org:
Univ. of Virginia, Charlottesville
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; CALCIUM COMPOUNDS; SECRETION; HORMONES; BIOLOGICAL EFFECTS; PHORBOL ESTERS; ANGIOTENSIN; BIOLOGICAL MODELS; CATIONS; HEPATECTOMY; INHIBITION; LIVER CELLS; PHOSPHATES; RATS; TOXINS; ALKALINE EARTH METAL COMPOUNDS; ANIMAL CELLS; ANIMALS; ANTIGENS; CARCINOGENS; CARDIOVASCULAR AGENTS; CHARGED PARTICLES; DRUGS; ESTERS; GLOBULINS; IONS; MAMMALS; MATERIALS; MEDICINE; ORGANIC COMPOUNDS; OXYGEN COMPOUNDS; PHOSPHORUS COMPOUNDS; PROTEINS; RODENTS; SOMATIC CELLS; SURGERY; TOXIC MATERIALS; VASOCONSTRICTORS; VERTEBRATES 560300* -- Chemicals Metabolism & Toxicology