Ca2+-independent phospholipase A2 is required for alpha 2-adrenergic-induced preadipocyte spreading

In the present study, we studied the involvement of A2 phospholipases (PLA2 ) in cua-adrenergic receptor-control of preadipocyte actin cytoskeleton. Fo r that, various PLA2 inhibitors were tested on the ability of the selective alpha 2-adrenergic agonist UK14304 to induce the spreading in alpha 2AF2 p readipocytes. We observed that, whereas several Ca2+-dependent PLA2 blocker s were ineffective, the Ca2+-independent phospholipase A2 (iPLA2) inhibitor , broenolactone (BEL), specifically blocked alpha 2-adrenergic-dependent pr eadipocyte spreading without affecting the spreading activity of lysophosph atidic acid (LPA) or serum. EEL inhibition was completely restored by lysop hosphatidic acid, but not by arachidonic acid or other fatty acids. The pre sence of the lysophospholipase (phospholipase B) suppressed the effect of L PA on preadipocyte spreading, but had no influence on alpha 2-adrenergic-in duced spreading. Thus, the extracellular production of LPA or fatty acids i s not involved in iPLA2-dependent preadipocyte spreading. iPLA2 protein was found in preadipocytes but, conversely to cPLA2, did not exhibit any modif ication of its electrophoretic mobility after alpha 2-adrenergic stimulatio n. We concluded that iPLA2 is involved in alpha 2-adrenergic control of pre adipocyte actin cytoskeleton. (C) 1999 Academic Press.