Receptor-coupled effector systems and their interactions

We investigated the modulation of intracellular signal generation by receptor-coupled effector systems in B lymphocytes, and whether these alterations are consistent with the effects of prostaglandins. TPA (12-O-tetradecanoyl phorbol-13-acetate) and sn-1,2,-dioctanoylglycerol (diC8) substitute for lipid derived signals which activate protein kinase C. Pretreating splenocytes from athymic nude mice with 100nM TPA or 5 μM diC8 potentiated the forskolin-induced increased in cAMP (measured by radioimmunoassay) 2.5 and 3.0 times (respectively), but they decreased the PGE1-induced cAMP rise 48% and 35% (respectively). Goat anti-mouse IgM, which activates diacylglycerol production, potentiated the forskolin-induced cAMP increase by 76%, but reduced that of PGE1 by 30%. Rabbit anti-mouse IgG, its F(ab')2 fragment, or goat anti-mouse IGM induced increases in the cytosolic free [Ca2+], [Ca2+]i, which TPA inhibited. In contrast, TPA potential antibody-induced 3H-thymidine (85x) and 3H-uridine (30x) uptake in B lymphocytes