EFFECTS OF PANCREATIC SPASMOLYTIC POLYPEPTIDE (PSP) ON EPITHELIAL-CELL FUNCTION

Trefoil peptides are expressed near endodermal ulcerations and may mod ulate epithelial repair. The trefoil pancreatic spasmolytic polypeptid e (PSP) was tested for growth activity in vitro on epithelial cells an d in vivo following intragastric or intravenous infusion in parenteral ly fed intact rats. Ion transport was assessed as changes in short-cir cuit current in rat intestine and adenocarcinoma cells in Ussing chamb ers. PSP stimulated growth of MCF-7 and Colo-357 cells, but only in th e presence of extracellular glutathione (GSH). The effect was attenuat ed by GSH depletion with buthionine sulphoximine, even in GSH-containi ng media. When GSH-reduced PSP was carboxymethylated with iodoacetic a cid, it still depended on extracellular GSH for its growth effect. Int estinal epithelial proliferation in rats was not affected by either in travenous or intraluminal infusion. PSP had no effect on basal or stim ulated ion flux in rat jejunum or epithelial monolayers. The peptide d id not compete with I-125-labeled epidermal growth factor for its rece ptor. [C-14]Iodoacetamide treatment of PSP, followed by prolonged tryp tic digestion yielded predominantly a C-14-labeled tetrapeptide fragme nt containing Cys104, with a lesser quantity of a C-14-labeled 15-amin o-acid peptide containing Cys95 (molar ratio 15:1). GSH may predominan tly reduce the Cys6-Cys104 terminal disulphide bond in PSP. We conclud e that some epithelia may exhibit a growth response to PSP if extracel lular GSH is present. Reduction of PSP by GSH is not necessary for thi s response, suggesting that the trefoil receptor or its signal transdu ction is GSH sensitive. PSP could assist wound healing by interactions with epithelial cells exposed concurrently to a local high GSH concen tration.