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...

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Published in:Alcohol (Fayetteville, N.Y.) N.Y.), 2016-11, Vol.56, p.1-8
Main Authors: Zhang, Yang, Xiu, Minghui, Jiang, Jinhong, He, Jianzheng, Li, Dongqin, Liang, Shiwei, Chen, Qiang
Format: Article
Language:English
Subjects:
Acids
Alcohol
Alcohol-induced ulceration
Animals
Antioxidants
Antisecretory
AT2 receptor
Dose-Response Relationship, Drug
Drugs
Ethanol
Ethanol - toxicity
Gastric Acid - secretion
Gastric Mucosa - drug effects
Gastric Mucosa - pathology
Gastric Mucosa - secretion
Gastroprotection
Injections, Intraventricular
Laboratories
Lipid peroxidation
Lipids
Male
Mucous membrane
Novokinin
Oligopeptides - administration & dosage
Pathogenesis
Peptides
Physiology
Psychiatry
Rats
Rats, Sprague-Dawley
Rodents
Studies
Ulcers
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Summary: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 100 nmol/rat. The effect of novokinin on gastric acid secretion was reversed by central injection of PD 123319 (10 nmol/rat), an AT2 receptor antagonist, and peripheral injection of indomethacin (10 mg/kg), an inhibitor of prostaglandin synthesis. Meanwhile, pre-treatment with novokinin at doses of 10, 50, and 100 nmol/rat significantly reduced the alcohol-induced gastric mucosal injury compared to the ulcer-control group, which was inhibited by indomethacin (10 mg/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.
ISSN:0741-8329
1873-6823
DOI:10.1016/j.alcohol.2016.08.003