The influence of brain inflammation upon neuronal adenosine A2B receptors.

Abstract

Alzheimer's disease (AD) is associated with glial activation and increased levels of pro-inflammatory cytokines. Epidemiological results suggest that anti-inflammatory therapies can slow the onset of AD. Adenosine, acting at type-2 receptors, is an effective endogenous anti-inflammatory agent that can modulate inflammation both in the periphery and the brain. We investigated changes in the expression of adenosine type-2B (A2B) receptors and a related intracellular second messenger during chronic brain inflammation and following treatment with the non-steroidal anti-inflammatory drug flurbiprofen and its nitric oxide (NO)-donating derivative, HCT1026. Chronic infusion of lipopolysaccharide (LPS) into the 4th ventricle of young rats induced brain inflammation that was associated with microglial activation and reduced neuronal immunoreactivity for adenosine A2B receptors in the cortex. Daily administration of HCT1026, but not flurbiprofen, reduced microglial activation, prevented the down-regulation of A2B receptors and elevated tissue levels of cAMP. The results suggest that a therapy using an NO-releasing NSAID might significantly attenuate the processes that drive the pathology associated with AD and that this process may involve the activation of adenosine A2B receptors.

• Authors: Susanna Rosi, Kristin McGann, Beatrice Hauss-Wegrzyniak, Gary L Wenk
• Journal: Journal of neurochemistry (J Neurochem) Vol. 86 Issue 1 Pg. 220-7 (Jul 2003) ISSN: 0022-3042 [Print] England
• PMID: 12807441 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Lipopolysaccharides
• Nitric Oxide Donors
• Receptor, Adenosine A2B
• Receptors, Purinergic P1
• nitroflurbiprofen
• Flurbiprofen

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Chronic Disease
• Disease Models, Animal
• Encephalitis (chemically induced, metabolism, pathology)
• Flurbiprofen (analogs & derivatives, pharmacology)
• Immunohistochemistry
• Lipopolysaccharides
• Male
• Microglia (drug effects, pathology)
• Neurons (drug effects, metabolism, pathology)
• Nitric Oxide Donors (pharmacology)
• Rats
• Rats, Inbred F344
• Receptor, Adenosine A2B
• Receptors, Purinergic P1 (metabolism)
• Second Messenger Systems (drug effects, physiology)