The role of peripheral serotonin and norepinephrine in the gastroprotective effect against stress of duloxetine

Ding, Hongwan; Gao, Yinge; Wang, Ying; Yao, Kaiyun; Wang, Guibin; Zhang, Jianjun

doi:10.1016/j.ejphar.2023.175499

Cited by 2 publications

(3 citation statements)

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“…Our previous study demonstrated that prophylactic protection of duloxetine against stress gastric ulcer depended on increasing the levels of serotonin in PPP and decreasing the levels of norepinephrine (Ding et al, 2023). We validated the effect of monoamines in the indomethacin-induced ulcer model and found the changes of serotonin influenced by duloxetine were consistent in two models.…”

Section: Discussionmentioning

confidence: 64%

“…The water immersion restraint stress (WIRS) procedure was performed as previous study (Ding et al, 2023). Before WIRS, rats were fasted for 30 hours but water was allowed.…”

Section: Water Immersion Restraint Stress-induced Gastric Ulcermentioning

confidence: 99%

“…The high performance liquid chromatography (HPLC) with electrochemical detection (ECD) method was performed as previously described (Ding et al, 2023).…”

Section: Analysis Of Neurotransmitters By High Performance Liquid Chr...mentioning

confidence: 99%

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The involvement of cytokines in the prophylactic effect of duloxetine on indomethacin-induced gastric ulcer

Ding,

Wang,

Gao

et al. 2023

Preprint

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Gastric ulcer is a common and global disease with high recurrence rate. It has been shown that selective serotonin-norepinephrine reuptake inhibitor duloxetine had protective effect on indomethacin-induced gastric ulcer, which was escorted by inflammation in the gastric mucosa. Cytokines, small-molecule peptides secreted from a variety of cells, are the principal mediators of inflammation. By screening the differential expression of cytokines in the gastric mucosa using cytokine array, we found that indomethacin induced increase in cytokines which promoted inflammation responses, whereas the protective effect of duloxetine was mediated through correcting the imbalance between pro-inflammatory cytokines and anti-inflammatory cytokines in gastric mucosa. Among them, RANTES was a key mediator in the prophylactic effect of duloxetine against indomethacin. We further identified that the protection was mediated by RANTES-chemokine receptor type 5 (CCR5) axis and inhibition of the axis by Met-Rantes or a CCR5 antagonist maraviroc suppressed the protection of duloxetine. Considering the pharmacologic action of duloxetine on reuptake of monoamine neurotransmitters, we examined the serotonin, norepinephrine and dopamine contents in the blood and discovered 20 mg/kg duloxetine increased serotonin levels in platelet-poor plasma, thus promoting expression of RANTES in gastric mucosa. Furthermore, increased RANTES activated PI3K-AKT-VEGF signaling pathway, which may be attributed to the protective effect of VEGF on endothelial cells and vessels in gastric mucosa. Together, our results identified the role of cytokines, particularly RANTES, and the underlying mechanisms in protection of duloxetine against indomethacin-induced gastric ulcer, which advanced our understanding in inflammatory modulation by monoamine-based antidepressant.

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Section: Discussionmentioning

confidence: 64%

“…The water immersion restraint stress (WIRS) procedure was performed as previous study (Ding et al, 2023). Before WIRS, rats were fasted for 30 hours but water was allowed.…”

Section: Water Immersion Restraint Stress-induced Gastric Ulcermentioning

confidence: 99%