Exendin Increases Gastric Acid Secretion in the Anesthetized Rat

Abstract

The objective of the current study was to assess the effect of the anti‐diabetic peptide, exenatide (Byetta®), on gastric acid secretion in the rat. Fasted rats were anesthetized and cannulas placed in esophagus (timed stomach secretion sampling), femoral artery (blood pressure monitoring), carotid artery (timed blood sampling). Phenol red was injected via the esophageal cannula and recovered every 10 minutes. Stomach aspirates were assessed for phenol red content (gastric emptying), pH, and titrated to pH 7.0 to calculate umoles of acid recovered. Exendin (up to 150 ug/kg) or vehicle were administered as a subcutaneous bolus at time zero, and stomach contents and blood were collected every 10 minutes for the subsequent 90 minutes. At 90 minutes, a pentagastrin bolus (~250 ug SC) was administered to confirm integrity of parietal cell responsiveness to pharmacologic stimulation of acid secretion. Basal acid secretion rate in the anesthetized rat (~1‐3 umoles per 10 minutes) was confirmed as lower than acid secretion rates previously reported in conscious rats. Exendin increased gastric acid secretion several‐fold above basal secretion rate, with maximal effect at 20‐30 minutes post‐injection. The anesthetized rat is a suitable model for assessing acute effects of peptides on stimulation of gastric acid secretion. The low basal acid secretion provides a substantial margin to successfully observe stimulation of acid secretion above an unstimulated baseline for at least 90 minutes. This model also allows simultaneous evaluation of hemodynamics and blood samples for pharmacokinetics and biomarker analysis.