title: Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons.
abstract: Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E2 (PGE2) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE2 induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE2 effect on visceral afferent sensory neurons of the rat. Interestingly, PGE2 itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE2-induced potentiation were blocked by a selective E-prostanoid type 4 (EP4) receptors antagonist, L-161,982, but type 1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE2 effects. PGE2 induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE2 potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin synthetase inhibitors by selectively targeting EP4 receptor/PKA pathway without interrupt prostaglandin synthesis.
authors.affiliation: Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Sojin
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Goeun
authors.initials: G
authors.lastname: Lee
authors.affiliation: Department of Microbiology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Yong Seek
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Microbiology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Cheung-Seog
authors.initials: CS
authors.lastname: Park
authors.affiliation: Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea. Electronic address: jinyh@khu.ac.kr.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Jin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005767:Gastrointestinal Diseases / Q000188:drug therapy; D007082:Ileum / Q000187:drug effects* / Q000294:innervation; D008297:Male; D009475:Neurons, Afferent / Q000378:metabolism; D009620:Nodose Ganglion / Q000187:drug effects*; D017294:Ondansetron / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011453:Prostaglandins / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction; D013270:Stomach / Q000187:drug effects* / Q000294:innervation; D013876:Thiophenes / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D017833:Visceral Afferents / Q000378:metabolism*; D044004:Xanthones / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D002227:Carbazoles; C508711:L-161982; D011453:Prostaglandins; D011758:Pyrroles; D044406:Receptors, Serotonin, 5-HT3; D013876:Thiophenes; D014230:Triazoles; D044004:Xanthones; D012701:Serotonin; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D017294:Ondansetron; C057416:KT 5720; D015232:Dinoprostone
keywords: E-prostanoid receptors; Gastrointestinal disorder; Prostaglandins; Serotonin; Visceral afferents neuron