cAMP potentiates beta-amyloid-induced nitric oxide release from microglia

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.