Effects of pancreatic spasmolytic polypeptide (PSP) on epithelial cell function

William R. Otto, Jagdish Rao, Helen M. Cox, Ewald Kotzian, Chung Y. Lee, Robert A. Goodlad, Andrew Lane, Michael Gorman, Paul A. Freemont, Hans F. Hansen, Darryl Pappin, Nicholas A. Wright

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Trefoil peptides are expressed near endodermal ulcerations and may modulate epithelial repair. The trefoil pancreatic spasmolytic polypeptide (PSP) was tested for growth activity in vitro on epithelial cells and in vivo following intragastric or intravenous infusion in parenterally fed intact rats. Ion transport was assessed as changes in short-circuit current in rat intestine and adenocarcinoma cells in Ussing chambers. PSP stimulated growth of MCF-7 and Colo-357 cells, but only in the presence of extracellular glutathione (GSH). The effect was attenuated by GSH depletion with buthionine sulphoximine, even in GSH-containing media. When GSH-reduced PSP was carboxymethylated with iodoacetic acid, it still depended on extracellular GSH for its growth effect. Intestinal epithelial proliferation in rats was not affected by either intravenous or intraluminal infusion. PSP had no effect on basal or stimulated ion flux in rat jejunum or epithelial monolayers. The peptide did not compete with 125I-labeled epidermal growth factor for its receptor. [14C]Iodoacetamide treatment of PSP, followed by prolonged tryptic digestion yielded predominantly a 14C-labeled tetrapeptide fragment containing Cys104, with a lesser quantity of a 14C-labeled 15-amino-acid peptide containing Cys95 (molar ratio 15:l). GSH may predominantly reduce the Cys6-Cys104 terminal disulphide bond in PSP. We conclude that some epithelia may exhibit a growth response to PSP if extracellular GSH is present. Reduction of PSP by GSH is not necessary for this response, suggesting that the trefoil receptor or its signal transduction is GSH sensitive. PSP could assist wound healing by interactions with epithelial cells exposed concurrently to a local high GSH concentration.

Original languageEnglish
Pages (from-to)64-72
Number of pages9
JournalEuropean Journal of Biochemistry
Issue number1-2
StatePublished - 1996


  • glutathione
  • pancreatic spasmolytic polypeptide
  • proliferation
  • short-circuit current
  • total parenteral nutrition
  • trefoil peptide

ASJC Scopus subject areas

  • Biochemistry


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