Apelin-12 stimulates acid secretion through an increase of histamine release in rat stomachs

Apelin is a peptide that was originally isolated from bovine stomach extract and has been demonstrated to be an endogenous ligand for orphan receptor APJ. Both apelin and the APJ receptor are widely distributed in the whole body. Apelin is supposed to have important regulatory roles in the function of many organs such as in the cardiovascular system; however, the mechanism of apelin function has not been elucidated. In this study, we studied the action of apelin in acid secretion and demonstrated its mechanism of action. Gastric lumen-perfused rats were prepared and their stomachs were perfused with a saline solution using a peristaltic pump. Apelin-12, 36 or Pyr1-apelin-13, were intravenously injected to examine their effects on acid secretion in rats. In some experiments, rats were pretreated with famotidine (0.33mg/kg) or atropine sulfate (0.1mg/kg) intravenously injected 5 or 15min before apelin injection. Furthermore, isolated vascularly perfused rat stomachs were prepared to examine the effect of apelin on histamine release, which was assayed in the effluent by radioimmunoassay. Messenger RNA of histidine decarboxylase (HDC) in gastric mucosa of isolated stomach was measured by real-time RT-PCR. Apelin-12 (20–100μg/kg) dose-dependently increased gastric acid secretion, with a maximum of 203% at 100μg/kg (n=5). Neither Pyr1-apelin-13 nor apelin-36 caused a significant increase in acid secretion. Famotidine completely blocked the stimulatory action of apelin on acid secretion. Apelin-12 (100μg/20ml/10min) markedly increased histamine release from isolated vascularly perfused rat stomachs by 278%, and also increased the mRNA of HDC by 480% of the control. Atropine sulfate did not abolish the effect of apelin on the secretion of gastric acid. Apelin-12 amplified an increase of acid secretion stimulated by gastrin injection. These results indicate that apelin-12 stimulates gastric acid secretion through an increase in histamine release and synthesis from gastric mucosa, suggesting that apelin might play a role in the secretion of gastric acid or serve as a regulating factor of the secretion of gastric acid. ► We studied the action of apelin-12 on the secretion of gastric acid. ► Apelin-12 increased acid output in gastric lumen-perfused rat stomachs. ► Famotidine, inhibited apelin-12-stimulated acid secretion. ► Apelin-12 stimulated histamine secretion and synthesis in rat stomachs. ► The results indicate that apelin plays a role in the secretion of gastri