Selective inhibition of duodenal and jejunal villous cell alkaline phosphatase by the duodenal ulcerogen cysteamine

I. Japundzic*, Lj Rakic-Stojiljkovic, E. Levi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

We have found that cysteamine-HCl, a potent duodenal ulcerogen, after a single subcutaneous injection (30mg/100g body weight), inhibited villous cell duodenal and jejunal alkaline phosphatase (APase) under in vivo and under in vitro conditions. The duodenal and jejunal crypt-cell APase was not susceptible to cysteamine inhibition. Ileal APase from both the villous and the crypt cells was unaffected by cysteamine. Tissue-nonspecific APase from the kidney and liver was not affected by cysteamine either. The differences in tissue and cellular accumulation of cysteamine, the submolecular differences in APase molecules, and its anatomical localization in mucosal cells along the small intestine could explain the different degrees of susceptibility to cysteamine inhibition. The extent of duodenal APase inhibition by cysteamine was highly pH-dependent and varied from 5 % to 85 % within a pH range of 7.5-10.5. A shift in pH optimum from 9.6 to 9.3 was found in the presence of cysteamine. The inhibition of duodenal villous cell APase was greatly dependent on cysteamine concentration (Ki = 2.65 mM). At a fixed concentration of cysteamine it was not influenced by substrate concentration. Cysteamine did not change the Km value for duodenal APase but did decrease its Vmax to 46 % and 15 % of the controls when added in the assay or injected subcutaneously, respectively, indicating that the inhibition was of the linear, 'noncompetitive' type. Somehow cysteamine increased the requirement in the activation energy for substrate hydrolysis as well. The data indicate that macromolecular transformations could take place in the mucosal cells of duodenum after cysteamine administration.

Original languageEnglish (US)
Pages (from-to)523-534
Number of pages12
JournalScandinavian Journal of Gastroenterology
Volume26
Issue number5
DOIs
StatePublished - 1991

Keywords

  • Alkaline phosphatase
  • Cysteamine
  • Duodenal ulcer
  • Enzyme inhibition
  • Intestinal villous cells

ASJC Scopus subject areas

  • Gastroenterology

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