Proliferation-dependent changes in arachidonic acid mobilization from phospholipids of 3T6 fibroblasts

Pflugers Arch. 1996 Aug;432(4):655-62. doi: 10.1007/s004240050182.


When we stimulated 3T6 fibroblasts, we observed a mobilization of arachidonic acid (AA) from phospholipids. The magnitude of this response decreased as the cells became confluent and the change coincided with a decrease in the percentage of cells in growth phases (G2 + M); this was not a consequence of the time in culture or a factor in the growth medium. Preconfluent fibroblasts incubated with the calcium ionophore A23187 (1 microM), 4beta-phorbol-12-myristate acetate (PMA, 10 microM), bradykinin (10 microM) or fetal calf serum (20%) released 38.8%, 62.5%, 11.2% and 45.6% [3H]AA, respectively. Confluent cells stimulated under the same conditions released only 16.9%, 1.5%, 0.5% and 18.5% [3H]AA, respectively. This decreasing mobilization of AA was demonstrated using metabolic labelling and measurement of prostaglandin PGE2. The decrease was not due to a changing pool of AA. [3H]AA release from each phospholipid decreased with confluence. Conversion of confluent cells to the proliferative phenotype by mechanical wounding of the monolayer increased the release of [3H]AA. This effect is consistent with regulated, growth-dependent changes in the activity of phospholipase A2, a process regulated by changes in phosphorylation of the enzyme. The increased release of [3H]AA from preconfluent, actively dividing cells may have important physiological implications and may help elucidate mechanisms regulating release of AA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acid / metabolism*
  • Bradykinin / pharmacology
  • Calcimycin / pharmacology
  • Cell Division / drug effects
  • Cell Line
  • Culture Media
  • Dinoprostone / biosynthesis
  • Enzyme Inhibitors / pharmacology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Mice
  • Okadaic Acid / pharmacology
  • Phospholipases A / metabolism
  • Phospholipases A2
  • Phospholipids / metabolism*
  • Phosphoric Monoester Hydrolases / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology


  • Culture Media
  • Enzyme Inhibitors
  • Phospholipids
  • Okadaic Acid
  • Arachidonic Acid
  • Calcimycin
  • Phospholipases A
  • Phospholipases A2
  • Phosphoric Monoester Hydrolases
  • Dinoprostone
  • Tetradecanoylphorbol Acetate
  • Bradykinin