Background  Orexin‐A is a novel peptide that appears to play a role in regulation of gastric acid secretion. However, little is known about sites of its action. In addition, evidences suggest that some of orexin‐A neurons respond to glucose. In this study, we address the hypothesis which demonstrates that orexin‐A and glucose act in the hypothalamic paraventricular nucleus (PVN) to increase gastric acid secretion and juice volume in pyloric‐ligated conscious rats.

Methods  Male Wistar rats were implanted with guide canula directed to the PVN. Orexin‐A (3–10 μg), glucose (350–750 ng) SB334867 (6–20 μg) were microinjected. The effect of pretreatment with an orexin‐1 receptor antagonist, SB334867, on orexin‐A and D‐glucose induced acid secretion was assessed. Gastric acid secretion was measured using the pylorus‐ligation method, and the amount of gastric acid was determined by titration with 0.01 N NaOH to a pH of 7.0.

Key Results  Intraparaventricular injection of orexin‐A or D‐glucose stimulated gastric acid secretion in a dose‐dependent manner. The PVN injections of orexin‐A receptor antagonist, SB334867, were associated with gastric acid secretion decrease and inhibited effects of PVN‐injected orexin‐A. Orexin‐stimulated gastric acid secretion was decreased (∼40%) after PVN lesions. Glucose‐stimulated gastric acid secretion was also suppressed by intraperitoneal (IP) injection of SB334867. In addition, it was observed that co‐injection of orexin‐A and glucose at ineffective doses increased gastric secretion significantly.

Conclusions & Inferences  We suggest that orexin‐A and glucose effects on the PVN stimulate gastric acid secretion. This stimulatory effect is probably mediated by orexin‐1 receptors.