Acute restraint stress induces cholecystokinin release via enteric apelin.

Stress increases the apelin content in gut, while exogenous peripheral apelin has been shown to induce cholecystokinin (CCK) release. The present study was designed to elucidate (i) the effect of acute stress on enteric production of apelin and CCK, (ii) the role of APJ receptors in apelin-induced CCK release depending on the nutritional status. CCK levels were assayed in portal vein blood samples obtained from stressed (ARS) and non-stressed (NS) rats previously injected with APJ receptor antagonist F13A or vehicle. Duodenal expressions of apelin, CCK and APJ receptor were detected by immunohistochemistry. ARS increased the CCK release which was abolished by selective APJ receptor antagonist F13A. The stimulatory effect of ARS on CCK production was only observed in rats fed ad-libitum. Apelin and CCK expressions were upregulated by ARS. In addition to the duodenal I cells, APJ receptor was also detected in CCK-producing myenteric neurons. Enteric apelin appears to regulate the stress-induced changes in GI functions through CCK. Therefore, apelin/APJ receptor systems seem to be a therapeutic target for the treatment of stress-related gastrointestinal disorders.