MEDULLARY THYROTROPIN-RELEASING-HORMONE MEDIATES VAGAL-DEPENDENT ADAPTIVE GASTRIC PROTECTION INDUCED BY MILD ACID IN RATS

Background & Aims: Adaptive gastric protection is dependent on vagal pathways in rats. It is hypothesized that medullary thyrotropin-releasing hormone (TRH), known to regulate vagal function, is part of the brain mechanisms mediating adaptive gastric protection. Methods: Urethane-anesthetized rats were pretreated with either acute bilateral subdiaphragmatic vagotomy, sham operation, or intracisternal injection of purified control, TRH, or peptide YY antibody. Gastric lesions were assessed 75 minutes after orogastric administration of 1 mL of either vehicle or 0.35N HCl followed 15 minutes later by 0.6N or 1.0N HCl. Results: Injection of 0.6N and 1.0N HCl induced gastric lesions covering 23.1% +/- 2.7% and 37.8% +/- 3.3% of the corpus mucosa, respectively. Pretreatment with 0.35N HCl resulted in 67.3% and 50.5% reductions in gastric lesions induced by 0.6N and 1.0N HCl, respectively. Subdiaphragmatic vagotomy or intracisternal injection of TRH antibody increased gastric lesions induced by 0.6N HCl to 32.2% +/- 2.2% and 42.9% +/- 5.6%, respectively, and completely abolished the protective effect of 0.35N HCl pretreatment. Control or peptide YY antibody injected intracisternally did not alter the gastric protection induced by mild acid. Conclusions: These results indicate that medullary TRH plays a role in the vagally mediated adaptive gastric protection induced by mild acid.