Mucosal secretion and cytoprotection of the rat gastric mucosa.
We carried out a series of experiments to test the hypothesis that many examples of gastric cytoprotection result from the ability of protective agents to elevate mucosal secretion. Specifically, such protection would be effective against barrier breakers that act directly on the mucosal surface. We have previously observed that the protection found to result, in our rat gastric chamber model, from luminal stasis or from sucralfate, was accompanied by increases in the thickness of a juxtamucosal pH gradient. The pH gradient was measured with antimony microelectrodes and was about 900 microns thick over chambered gastric mucosae that had not had the luminal solution stirred for at least 5 min. When the solution was stirred (200 rpm) for 10 min with a plastic paddle, the thickness of the pH gradient was decreased to about 400 microns but recovered to more than 90% of the starting value within 5 min. The thickness of the pH gradient varied from site to site, with a range from about 500 microns to 1,800 microns. However, the thickness was constant at a given site when it was remeasured after about 1 h. Capsaicin at a concentration of 640 microM rapidly increased both gastric blood flow and the thickness of the juxtamucosal pH gradient by about 50%. However, 25 min after removal of the capsaicin the gastric blood flow approached pre-capsaicin levels, and the thickness of the gradient remained increased by nearly 50%. In a third set of experiments, the vulnerability of specific sites on the chambered mucosae to acidified sodium taurocholate was correlated with the thickness of the juxtamucosal pH gradient before exposure to taurocholate.(ABSTRACT TRUNCATED AT 250 WORDS)
Morris
G P
GP
Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada.
Basu
B K
BK
Holitzner
C A
CA
Williamson
T E
TE
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity; D005260:Female; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D006851:Hydrochloric Acid / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008353:Mannitol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013392:Sucralfate / Q000494:pharmacology*
D000431:Ethanol; D008353:Mannitol; D013392:Sucralfate; D006851:Hydrochloric Acid; D002211:Capsaicin