Exocrine secretion and processing of pro-xenopsin in rat gastric lumen

This study examines the effects of acid, acid secretagogues, and pepstatin on gastric luminal concentrations of xenopsin-like immunoreactivity (XPLI) by in situ luminal perfusion of the stomach in anesthetized rats. During perfusion with saline over a 2-h period, the concentration of XPLI fell in parallel with acid output. Levels of XPLI fell more rapidly when the saline contained 20 micrograms/ml pepstatin A and when phosphate-buffered saline (pH 7.0) was used. These treatments did not, however, alter acid output. After a basal condition was established at 90 min, intravenous injection of carbachol, pentagastrin, or histamine stimulated acid and pepsin secretion and also led to an increase in XPLI concentration, which was pepstatin sensitive. Acid itself was also a stimulus for pepsin and XPLI output, which were correlated at various levels of acidity. Although pepstatin blocked the effect of acid on XPLI output, it did not lead to an accumulation of xenopsin (XP) precursor in the luminal fluid. However, the decrement in acid-stimulated XPLI output seen in the presence of pepstatin was matched by an increment in XP precursor associated with the mucosal surface. During high-pressure liquid chromatography, approximately 70% of the acid-generated XPLI eluted at the position of mammalian XP. These data support the notion that, during heightened acid output, XP is secreted by a pepsin-dependent process or generated by the action of pepsin on XP precursor present on the mucosal surface of the rat stomach.