ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract : Prostaglandins (PGs) are potent modulators of brainfunction under normal and pathological conditions. The diverse effects of PGsare due to the various actions of specific receptor subtypes for theseprostanoids. Recent work has shown that PGE2, while generallyconsidered a proinflammatory molecule, reduces microglial activation and thushas an antiinflammatory effect on these cells. To gain further insight to themechanisms by which PGE2 influences the activation of microglia, weinvestigated PGE receptor subtype, i.e., EP1, EP2, EP3, and EP4, expressionand function in cultured rat microglia. RT-PCR showed the presence of the EP1and EP2 but not EP3 and EP4 receptor subtypes. Sequencing confirmed theiridentity with previously published receptor subtypes. PGE2 and theEP1 agonist 17-phenyl trinor PGE2 but not the EP3 agonistsulprostone elicited reversible intracellular [Ca2+] increases inmicroglia as measured by fura-2. PGE2 and the EP2/EP4-specificagonists 11-deoxy-PGE1 and 19-hydroxy-PGE2 but not theEP4-selective agonist 1-hydroxy-PGE1 induced dose-dependentproduction of cyclic AMP (cAMP). Interleukin (IL)-1β production, a markerof activated microglia, was also measured following lipopolysaccharideexposure in the presence or absence of the receptor subtype agonists.PGE2 and the EP2 agonists reduced IL-1β production. IL-1βproduction was unchanged by EP1, EP3, and EP4 agonists. The adenylyl cyclaseactivator forskolin and the cAMP analogue dibutyryl cAMP also reducedIL-1β production. Thus, the inhibitory effects of PGE2 onmicroglia are mediated by the EP2 receptor subtype, and the signalingmechanism of this effect is likely via cAMP. These results show that theeffects of PGE2 on microglia are receptor subtype-specific. Furthermore, they suggest that specific and selective manipulation of the effects of PGs on microglia and, as a result, brain function may be possible.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.1999.0720565.x
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