INCREASED CYCLIC-AMP RESPONSE TO FORSKOLIN IN EPSTEIN-BARR VIRUS-TRANSFORMED HUMAN B-LYMPHOCYTES DERIVED FROM SCHIZOPHRENICS

Phorbol 12-myristate-13-acetate (PMA), a protein kinase C (PKC) activa tor, elevated basal cyclic AMP levels and enhanced isoproterenol-, pro staglandin E-1- (PGE(1)), forskolin- and cholera toxin-stimulated cycl ic AMP accumulation in Epstein-Barr virus (EBV)-transformed human B-ly mphocytes. Staurosporine, a PKC inhibitor, significantly antagonized t he increase in cyclic AMP accumulation produced by PMA, whereas the in active phorbol ester, 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD), had no effect. Basal levels of cyclic AMP and the accumulation of cyc lic AMP produced by PMA, isoproterenol, PGE(1), cholera toxin and the combination of these compounds with PMA were not significantly differe nt between schizophrenics and controls. The cyclic AMP response to for skolin in the presence and absence of PMA was significantly greater in EBV-transformed human B-lymphocytes from schizophrenics. These result s suggest that activation of adenylyl cyclase by forskolin is elevated in EBV-transformed B-lymphocytes derived from schizophrenics and that this elevation is further enhanced through a PKC-dependent phosphoryl ation mechanism.