Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons
Journal Article
·
· Biochemical and Biophysical Research Communications
- Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of)
- Department of Microbiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of)
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.
- DOE Contract Number:
- ;
- OSTI ID:
- 22416872
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 456; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
Similar Records
Prostaglandin F{sub 2{alpha}} regulates cytokine responses of mast cells through the receptors for prostaglandin E
Ciproxifan, a histamine H{sub 3} receptor antagonist and inverse agonist, presynaptically inhibits glutamate release in rat hippocampus
Threshold and Receptor Reserve in the Action of Neurohypophyseal Peptides. A study of synergists and antagonists of the hydroosmotic response of the toad urinary bladder
Journal Article
·
Fri Mar 14 00:00:00 UTC 2008
· Biochemical and Biophysical Research Communications
·
OSTI ID:21043656
Ciproxifan, a histamine H{sub 3} receptor antagonist and inverse agonist, presynaptically inhibits glutamate release in rat hippocampus
Journal Article
·
Wed Mar 15 00:00:00 UTC 2017
· Toxicology and Applied Pharmacology
·
OSTI ID:22690938
Threshold and Receptor Reserve in the Action of Neurohypophyseal Peptides. A study of synergists and antagonists of the hydroosmotic response of the toad urinary bladder
Journal Article
·
Sat Aug 01 00:00:00 UTC 1970
· Journal of General Physiology
·
OSTI ID:1629139