PHOSPHATIDYLCHOLINES AS MEDIATORS OF ADAPTIVE CYTOPROTECTION OF THE RAT DUODENUM

Background/Aims: Surfactant phospholipids impede diffusion of acid through the gastric mucus, but their relevance in the defense of the duodenum against luminal acid is not known. Methods: Duodenal resistance to acid was tested in anesthetized rats by instillation of HCI using a tube implanted in the proximal duodenum. The effects of a detergent (Brij 35; Sigma, St. Louis, MO) and a lipid mixture flushed through the luminal surface on duodenal resistance to acid were studied. The lipid content in the mucus and the effects of acid, prostaglandins, and indomethacin on the lipid layer were also analyzed. Results: Instillation of 100 μmol HCI or 5 μg/kg 16,16-dimethyl prostaglandin E2 increased resistance to acid, preventing duodenal lesions induced by 500 umol HCI. However, 100 μmol HCI or 16,16-dimethyl prostaglandin E2 did not prevent lesions induced by 500 umol HCI in rats undergoing perfusions with 5% Brij 35. Indomethacin suppressed acid-induced protection. A mixture of tripalmitin and dipalmitoyl-phosphatidylcholine protected against 500 umol HCI, and the effect was also observed in rats receiving indomethacin. Finally, 100 μmol HCI increased the phosphatidylcholine content in the duodenal mucus but not in rats receiving 5% Brij 35 or indomethacin. Conclusions: Surface-active phospholipids are critical for adaptive cytoprotection to acid in the rat duodenum. © 1994.