LP44 (4-[2-(methylthio)phenyl]-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanamide) exerts anti-ulcer effects via 5-hydroxytryptamine receptor 7 activation on indomethacin-induced gastric ulcers in rats.

AIM

This study aimed to demonstrate the role of serotonin 7 receptor (5-HT) and the effects of 5-HT agonists and antagonists in an indomethacin-induced gastric ulcer.

MATERIAL AND METHOD

Male albino Wistar rats (n = 60) were used in the experiments. LP44 (5-HT agonist) and SB269970 (5-HT antagonist) were administered at 10 mg/kg as a pre-treatment. One hour after the drug treatments, 25 mg/kg of indomethacin (INDO) was administered to all groups except the healthy control group. Six hours after indomethacin administration, all the rats were euthanized.

RESULTS

We analyzed the iNOS, eNOS, and 5-HT receptor mRNA levels in the stomach tissue of rats by real-time PCR. 5-HT mRNA expression was increased in the INDO group compared to the healthy group. LP44 administration exerted a significant upregulatory effect on eNOS mRNA expression and downregulatory effects on iNOS and 5-HT mRNA expression compared to the INDO group. However, antagonist (SB269970) administration did not result in such difference in gene expression, but even partially decreased the agonist's effect in combination. Famotidine and agonist exerted similar effects. Histopathological findings supported the beneficial effects of 5-HT agonist on gastric tissue.

CONCLUSION

The study suggested that activation of 5-HT receptor showed a significant anti-ulcerogenic effect in the indomethacin-induced gastric ulcer model.