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Title: Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons

Abstract

Highlights: • Prostaglandin E2 (PGE{sub 2}) effect was tested on visceral afferent neurons. • PGE{sub 2} did not evoke response but potentiated serotonin (5-HT) currents up to 167%. • PGE{sub 2}-induced potentiation was blocked by E-prostanoid type 4 receptors antagonist. • PGE{sub 2} effect on 5-HT response was also blocked by protein kinase A inhibitor KT5720. • Thus, PGE{sub 2} modulate visceral afferent neurons via synergistic signaling with 5-HT. - Abstract: Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E{sub 2} (PGE{sub 2}) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE{sub 2} induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE{sub 2} effect on visceral afferent sensory neurons of the rat. Interestingly, PGE{sub 2} 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 PGE{sub 2}-induced potentiation were blocked by a selective E-prostanoid type4 (EP{sub 4}) receptors antagonist, L-161,982, but type1 andmore » 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE{sub 2} effects. PGE{sub 2} 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 PGE{sub 2} 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 EP{sub 4} receptor/PKA pathway without interrupt prostaglandin synthesis.« less

Authors:
; ;  [1]; ;  [2];  [1]
  1. Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of)
  2. Department of Microbiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of)
Publication Date:
OSTI Identifier:
22416872
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 456; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIPHENYL; CARBOXYLIC ACIDS; CELL MEMBRANES; CHEMOTHERAPY; EPOXIDES; ESTERS; IRRADIATION; LIGASES; NERVE CELLS; PERCHLORATES; PROSTAGLANDINS; RATS; RECEPTORS; SEROTONIN; SIDE EFFECTS; SMALL INTESTINE; STOMACH; SYMPTOMS; SYNTHESIS

Citation Formats

Kim, Sojin, Jin, Zhenhua, Lee, Goeun, Park, Yong Seek, Park, Cheung-Seog, and Jin, Young-Ho. Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2014.11.053.
Kim, Sojin, Jin, Zhenhua, Lee, Goeun, Park, Yong Seek, Park, Cheung-Seog, & Jin, Young-Ho. Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons. United States. https://doi.org/10.1016/J.BBRC.2014.11.053
Kim, Sojin, Jin, Zhenhua, Lee, Goeun, Park, Yong Seek, Park, Cheung-Seog, and Jin, Young-Ho. 2015. "Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons". United States. https://doi.org/10.1016/J.BBRC.2014.11.053.
@article{osti_22416872,
title = {Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons},
author = {Kim, Sojin and Jin, Zhenhua and Lee, Goeun and Park, Yong Seek and Park, Cheung-Seog and Jin, Young-Ho},
abstractNote = {Highlights: • Prostaglandin E2 (PGE{sub 2}) effect was tested on visceral afferent neurons. • PGE{sub 2} did not evoke response but potentiated serotonin (5-HT) currents up to 167%. • PGE{sub 2}-induced potentiation was blocked by E-prostanoid type 4 receptors antagonist. • PGE{sub 2} effect on 5-HT response was also blocked by protein kinase A inhibitor KT5720. • Thus, PGE{sub 2} modulate visceral afferent neurons via synergistic signaling with 5-HT. - Abstract: Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E{sub 2} (PGE{sub 2}) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE{sub 2} induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE{sub 2} effect on visceral afferent sensory neurons of the rat. Interestingly, PGE{sub 2} 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 PGE{sub 2}-induced potentiation were blocked by a selective E-prostanoid type4 (EP{sub 4}) receptors antagonist, L-161,982, but type1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE{sub 2} effects. PGE{sub 2} 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 PGE{sub 2} 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 EP{sub 4} receptor/PKA pathway without interrupt prostaglandin synthesis.},
doi = {10.1016/J.BBRC.2014.11.053},
url = {https://www.osti.gov/biblio/22416872}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 456,
place = {United States},
year = {Fri Jan 02 00:00:00 EST 2015},
month = {Fri Jan 02 00:00:00 EST 2015}
}