THE beta-amyloid peptide (A beta) has been known to activate microglia and
to induce release of nitric oxide (NO). In this study, we examined the effe
ct of cAMP on A beta-induced microglial activation using cultured rat brain
microglia. Dibutyryl-cAMP (dbcAMP) and 3-isobutyl-1-methylxanthine (IBMX)
significantly potentiated A beta(25-35)- or A beta(1-42)-induced NO release
in a dose-dependent manner. The increase in NO release was due to the incr
eased expression of inducible nitric oxide synthase (iNOS). However, forsko
lin, an adenylate cyclase activator, weakly increased NO release at 10-50 m
u M but caused a decrease at 100 mu M. These results suggest that increase
in intracellular cAMP could potentiate microglial activation induced by A b
eta. (C) 1999 Lippincott Williams & Wilkins.