Novokinin inhibits gastric acid secretion and protects against alcohol-induced gastric injury in rats.

Abstract

Novokinin (Arg-Pro-Leu-Lys-Pro-Trp), a potent vasorelaxing and hypotensive peptide modified from ovokinin, exhibits highly selective affinity for the AT2 receptor. However, its role in gastrointestinal functions is still not fully understood. In this study, we found that novokinin inhibited basal gastric acid secretion and protected gastric mucosa from alcohol-induced injury in a dose-related manner in rats after intracerebroventricular (i.c.v.) administration. Novokinin significantly decreased basal gastric acid output at the dose of 50 and 100nmol/rat. The effect of novokinin on gastric acid secretion was reversed by central injection of PD 123319 (10nmol/rat), an AT2 receptor antagonist, and peripheral injection of indomethacin (10mg/kg), an inhibitor of prostaglandin synthesis. Meanwhile, pre-treatment with novokinin at doses of 10, 50, and 100nmol/rat significantly reduced the alcohol-induced gastric mucosal injury compared to the ulcer-control group, which was inhibited by indomethacin (10mg/kg). The result showed a remarkable increase in the level of prostaglandin E2 (PGE2), glutathione (GSH), and a decrease in malondialdehyde (MDA) after i.c.v. administration of novokinin. These findings suggest that the inhibitory effect of novokinin on gastric acid secretion is probably mediated via an AT2 receptor-prostaglandins (PGs) pathway. The gastroprotective effect of novokinin might be attributed to the inhibition of acid secretion, the cytoprotection of PGs, and the antioxidant property.