Prostaglandin E2 attenuates preoptic expression of GABAA receptors via EP3 receptors.
Prostaglandin E(2) (PGE(2)) 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 PGE(2)-induced gene expression changes at single-cell resolution in preoptic neurons expressing EP3. Brain sections of the preoptic area from PGE(2)- 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 gamma-aminobutyric acid type A (GABA(A)) receptor subunits is decreased upon PGE(2) injection. Indeed, we found that most EP3-positive neurons in the mouse preoptic area are positive for the alpha2 or gamma2 GABA(A) receptor subunit. Moreover, PGE(2) decreased the preoptic gene expression of these GABA(A) subunits via an EP3-dependent and pertussis toxin-sensitive pathway. PGE(2) also attenuated the preoptic protein expression of the alpha2 subunit in wild-type but not in EP3-deficient mice. These results indicate that PGE(2)-EP3 signaling elicits G(i/o) activation in preoptic thermocenter neurons, and we propose the possibility that a rapid decrease in preoptic GABA(A) expression may be involved in PGE(2)-induced fever.
Tsuchiya
Hiroyoshi
H
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences and Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Oka
Takakazu
T
Nakamura
Kazuhiro
K
Ichikawa
Atsushi
A
Saper
Clifford B
CB
Sugimoto
Yukihiko
Y
D000818:Animals; D001921:Brain / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D058308:Receptors, Prostaglandin E, EP3 Subtype; D015398:Signal Transduction
C545648:Ptger3 protein, mouse; D011963:Receptors, GABA-A; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D015232:Dinoprostone