Prostaglandin E2 Attenuates Preoptic Expression of GABAA Receptors via EP3 Receptors

Prostaglandin E2 (PGE2) has been shown to produce fever by acting on EP3 receptors within the preoptic area of the brain. However, there is little information about the molecular events downstream of EP3 activation in preoptic neurons. As a first step toward this issue, we examined PGE2-induced gene...

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Bibliographic Details
Published in:The Journal of biological chemistry 2008-04, Vol.283 (16), p.11064-11071
Main Authors: Tsuchiya, Hiroyoshi, Oka, Takakazu, Nakamura, Kazuhiro, Ichikawa, Atsushi, Saper, Clifford B., Sugimoto, Yukihiko
Format: Article
Language:English
Subjects:
Animals
Brain - metabolism
Dinoprostone - metabolism
Male
Mice
Mice, Inbred C57BL
Microscopy, Fluorescence
Models, Biological
Neurons - metabolism
Oligonucleotide Array Sequence Analysis
Rats
Rats, Sprague-Dawley
Receptors, GABA-A - metabolism
Receptors, Prostaglandin E - metabolism
Receptors, Prostaglandin E, EP3 Subtype
Signal Transduction
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Summary:Prostaglandin E2 (PGE2) has been shown to produce fever by acting on EP3 receptors within the preoptic area of the brain. However, there is little information about the molecular events downstream of EP3 activation in preoptic neurons. As a first step toward this issue, we examined PGE2-induced gene expression changes at single-cell resolution in preoptic neurons expressing EP3. Brain sections of the preoptic area from PGE2- or saline-injected rats were stained with an anti-EP3 antibody, and the cell bodies of EP3-positive neurons were dissected and subjected to RNA amplification procedures. Microarray analysis of the amplified products demonstrated the possibility that gene expression of γ-aminobutyric acid type A (GABAA) receptor subunits is decreased upon PGE2 injection. Indeed, we found that most EP3-positive neurons in the mouse preoptic area are positive for the α2 or γ2 GABAA receptor subunit. Moreover, PGE2 decreased the preoptic gene expression of these GABAA subunits via an EP3-dependent and pertussis toxin-sensitive pathway. PGE2 also attenuated the preoptic protein expression of the α2 subunit in wild-type but not in EP3-deficient mice. These results indicate that PGE2-EP3 signaling elicits Gi/o activation in preoptic thermocenter neurons, and we propose the possibility that a rapid decrease in preoptic GABAA expression may be involved in PGE2-induced fever.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M801359200