Pancreatic spasmolytic polypeptide protects the gastric mucosa but does not inhibit acid secretion or motility.
The objectives of these studies were to examine whether the trefoil peptide porcine pancreatic spasmolytic polypeptide (PSP) had gastric mucosal protectant properties similar to its human equivalent human spasmolytic polypeptide (hSP) and to confirm the antisecretory and antimotility action of the peptide. PSP and recombinant hSP reduced gastric mucosal damage caused by a combination of subcutaneous indomethacin and restraint stress in the conscious rat. At a dose of 500 micrograms/kg bolus plus 500 micrograms.kg-1.h-1 sc, PSP significantly reduced the total area of damage by 58%. PSP at a dose of 150 micrograms/kg iv had no inhibitory effect on pentagastrin-stimulated gastric acid secretion in the perfused 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 inhibit electrically or chemically evoked contractions of the guinea pig ileum and duodenum in vitro. Thus antisecretory and antimotility actions do not underlie the mucosal protectant properties of PSP. PSP did, however, stimulate cell migration, and this may, at least in part, account for its protectant properties.
McKenzie
C
C
Gastrointestinal Pharmacology Unit, University of Hertfordshire, Hatfield, United Kingdom.
Marchbank
T
T
Playford
R J
RJ
Otto
W
W
Thim
L
L
Parsons
M E
ME
D000818:Animals; D002460:Cell Line; D003110:Colonic Neoplasms; D004558:Electric Stimulation; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000037:antagonists & inhibitors / Q000633:toxicity; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010276:Parasympatholytics / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D013552:Swine; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D014407:Tumor Cells, Cultured
D036341:Intercellular Signaling Peptides and Proteins; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010276:Parasympatholytics; D010455:Peptides; D011994:Recombinant Proteins; C099037:TFF3 protein, rat; C000604008:Tff2 protein, rat; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; C034407:pancreatic spasmolytic polypeptide; D007213:Indomethacin