PANCREATIC SPASMOLYTIC POLYPEPTIDE PROTECTS THE GASTRIC-MUCOSA BUT DOES NOT INHIBIT ACID-SECRETION OR MOTILITY

The objectives of these studies mere to examine whether the trefoil pe ptide porcine pancreatic spasmolytic polypeptide (PSP) had gastric muc osal protectant properties similar to its human equivalent human spasm olytic polypeptide (hSP) and to confirm the antisecretory and. antimot ility action of the peptide. PSP and recombinant hSP reduced gastric m ucosal damage caused by a combination of subcutaneous indomethacin and restraint stress in the conscious rat. At a dose of 500 mu g/kg bolus plus 500 mu g.kg(-1).h(-1) sc, PSP significantly reduced the total ar ea of damage by 58%. PSP at a dose of 150 mu g/kg iv had no inhibitory effect on pentagastrin-stimulated gastric acid secretion in the perfu sed stomachs of anesthetized rats. This lack of antisecretory activity was confirmed in vitro using an isolated stomach preparation from the immature rat. PSP and hSP at concentrations up to 800 nM did not inhi bit electrically or chemically evoked contractions of the guinea pig i leum and duodenum in vitro. Thus antisecretory and antimotility action s do not underlie the mucosal protectant properties of PSP. PSP did, h owever, stimulate cell migration, and this may, at least in part, acco unt for its protectant properties.