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) activator, elevated basal cyclic AMP levels and enhanced isoproterenol-, prostaglandin E1- (PGE1), forskolin- and cholera toxin-stimulated cyclic AMP accumulation in Epstein-Barr virus (EBV)-transformed human B-lymphocytes. Staurosporine, a PKC inhibitor, significantly antagonized the increase in cyclic AMP accumulation produced by PMA, whereas the inactive phorbol ester, 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD), had no effect. Basal levels of cyclic AMP and the accumulation of cyclic AMP produced by PMA, isoproterenol, PGE1, cholera toxin and the combination of these compounds with PMA were not significantly different between schizophrenics and controls. The cyclic AMP response to forskolin in the presence and absence of PMA was significantly greater in EBV-transformed human B-lymphocytes from schizophrenics. These results 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 phosphorylation mechanism.
Natsukari
N
N
National Institute of Mental Health, Neuropsychiatry Branch, Washington, DC 20032, USA.
Kulaga
H
H
Baker
I
I
Wyatt
R J
RJ
Masserano
J M
JM
D000328:Adult; D000527:Alprostadil / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002472:Cell Transformation, Viral / Q000187:drug effects*; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis*; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D012559:Schizophrenia / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D005576:Colforsin; D002772:Cholera Toxin; D000242:Cyclic AMP; D000527:Alprostadil; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate