Research Project
Grant-in-Aid for Scientific Research (B)
The purpose of this study is to understand the molecular mechanisms underlying prostanoid-induced and prostanoid receptor-mediated physiological actions.(1) Prostaglandin E_2 (PGE_2) plays a primary role in maintaining the patency of the ductus arteriosus (DA). EP4 deficiency, however, paradoxically results in fatal patent DA in mice. We found that EP4-mediated signals promote DA closure by hyaluronic acid (HA)-mediated intimal cushion formation. Chronic EP4 stimulation enhanced migration and HA production in DA smooth muscle cell, and activation of EP4 and protein kinase A increased HA Synthase (HAS)-2 transcripts. In immature rat DA explants, intimal cushion formation was promoted by EP4 stimuli. HAS2 gene transfer was sufficient to induce intimal cushion formation in EP4-deficient DA explants. Thus, EP4 has two essential roles in DA development, vascular dilation and intimal cushion formation. The latter action presumably facilitates luminal narrowing leading to adhesive occlusion a … More nd permanent closure of the vascular lumen.(2) PGE_2 has been shown to produce fever by acting on EP3 receptors within 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 to approach this issue, we examined PGE_2-induced gene expression changes at single cell resolution in preoptic neurons expressing EP3. Microarray analysis of EP3-positive neurons indicated that gene expression of gamma-aminobutyric acid type A receptor (GABA_A) is decreased upon PGE_2 injection. Indeed, most EP3-positive neurons in the preoptic area are positive for the GABA_A. PGE_2 decreased the preoptic gene expression of GABA_A via EP3-dependent and pertussis toxin-sensitive pathway. PGE_2 attenuated the preoptic protein expression of GABA_A in wild-type but not in EP3-deficient mice. Thus, PGE_2-EP3 signaling elicits G_<i/o> activation in preoptic thermocenter neurons and a rapid decrease in preoptic GABA_A expression may be involved in PGE_2-induced fever. Less
All 2008 2007 2006
All Journal Article (28 results) (of which Peer Reviewed: 12 results) Presentation (12 results) Patent(Industrial Property Rights) (1 results)
J. Biol. Chem. 283
Pages: 11064-11071
J. Pharmacol. Exp. Ther. (印刷中)
Biol. Reprod. 78
Pages: 438-444
Mol. Cell. Endocrinol. 283
Pages: 32-37
J. Biol. Chem 283
J. Pharmacol. Exp. Ther (in press)
Biol. Reprod 78
Mot Cell. Endocrinol 283
J. Biol. Chem. 283(印刷中)
J. Biol. Chem. 282
Pages: 32676-32688
Histochem. Cell Biol. 128
Pages: 317-322
Pages: 11613-11617
Am. J. Physiol. Endocrinol. metab. 292
J. Biol. Chem 282
Histochem. Cell Biol 128
J. Biol. Chem 282(16)
Am. J. Physiol. Endocrinol. Metab 292
Pages: 992-999
Am. J. Physiol. Endocrinol. Metab. 292
J. Immunol. 178
Pages: 7042-7053
J. Clin. Invest. 116
Pages: 3026-3034
Pediatr. Res. 60
Pages: 669-674
J. Obstet. Gynaecol. Res. 32
Pages: 373-378
J. Clin. Invest 116
Pediatr. Res 60
J. Obstet. Gynaecol. Res 32
J. Obstet, Gynaecol. Res. 32
