title: Potentiating effects of hyper-osmolality and epidermal growth factor on the release of arachidonic acid in human glomerular mesangial cells.
abstract: Studies were performed to determine the interactive effects of high concentrations of glucose (HG) and epidermal growth factor (EGF) on the release of arachidonic acid (3H-AA) in human glomerular mesangial cells (MC) in culture. Since high glucose has been reported to increase the mass of diacylglycerol (DAG) in MC, the HG-induced release of 3H-AA was compared to that initiated by the phorbol ester, PMA. It was found that when media contained high levels (25 mM) of glucose, the release of 3H-AA was increased significantly by 8.4% (change from control) after 1 h of exposure and was maintained at values not significantly different from this level for the next 2 h. After 3-h exposure, there was no significant difference between 25 and 50 mM glucose, suggesting that the effects of glucose are saturating at 25 mM. After 1-h exposure, 3H-AA release was also increased by PMA; however, the increase was larger and the peak increase was delayed until after 1 h. 3H-AA release was significantly increased by epidermal growth factor (EGF) by 8.5% after 1 h and was maintained at this level after 2 and 3 h of exposure. In the presence of HG, EGF increased 3H-AA release by 24.6% after the 1st hour and by 20.4 and 19.4%, after the 2nd and 3rd hours, respectively. Mannitol (20 mM), added as an osmotic control, increased 3H-AA release by 6.2% and also significantly enhanced the effects of EGF after 3 h. The experimental values (19.0%) for the release of 3H-AA after 3-h exposure to EGF in combination with either high glucose or mannitol were significantly greater than the expected (added) values (12.1%). These results demonstrate that as a result of an elevated solution osmolality, high glucose acts synergistically with EGF to increase the release of 3H-AA in human mesangial cells.
authors: Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198-4575, USA.
authors: S C
authors: SC
authors: Sansom
authors: P
authors: P
authors: Mehta
authors: D A
authors: DA
authors: Hall
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D008353:Mannitol / Q000494:pharmacology; D009994:Osmolar Concentration; D012996:Solutions / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D012996:Solutions; D016718:Arachidonic Acid; D008353:Mannitol; D004815:Epidermal Growth Factor; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate