cAMP potentiates beta-amyloid-induced nitric oxide release from microglia.
The beta-amyloid peptide (Abeta) has been known to activate microglia and to induce release of nitric oxide (NO). In this study, we examined the effect of cAMP on Abeta-induced microglial activation using cultured rat brain microglia. Dibutyryl-cAMP (dbcAMP) and 3-isobutyl-1-methylxanthine (IBMX) significantly potentiated Abeta(25-35)- or Abeta(1-42)-induced NO release in a dose-dependent manner. The increase in NO release was due to the increased expression of inducible nitric oxide synthase (iNOS). However, forskolin, an adenylate cyclase activator, weakly increased NO release at 10-50 microM but caused a decrease at 100 microM. These results suggest that increase in intracellular cAMP could potentiate microglial activation induced by Abeta.
Pyo
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Department of Pharmacology, Ajou University School of Medicine, Suwon, Kyunggi-do, Korea.
Jou
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Jung
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Joe
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000187:drug effects; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D004357:Drug Synergism; D004789:Enzyme Activation; D017628:Microglia / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D005576:Colforsin; D009569:Nitric Oxide; D003994:Bucladesine; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000262:Adenylyl Cyclases; D015056:1-Methyl-3-isobutylxanthine