Prostaglandins inhibit inflammatory mediator release from rat mast cells.
BACKGROUND
Mast cells have been implicated in the pathogenesis of gastric ulceration. It is possible that prostaglandins exert cytoprotective effects by inhibiting the release of proulcerogenic mediators from mast cells.


METHODS
The effects of three prostaglandins on the release of platelet-activating factor, tumor necrosis factor, and histamine from rat mast cells (peritoneal and intestinal mucosal) activated with calcium ionophore or antigen were assessed.


RESULTS
Upon stimulation with either agonist, intestinal mucosal and peritoneal mast cells released significant quantities of platelet-activating factor. Preincubation for 5 minutes with misoprostol, prostaglandin (PG)E2, 16,16-dimethyl PGE2, ketotifen, or PF-5901 concentration-dependently reduced ionophore-stimulated platelet-activating factor release; significant effects were observed with picomolar to nanomolar concentrations of the prostaglandins and micromolar concentrations of the other compounds. Tumor necrosis factor release from peritoneal and mucosal mast cells was also significantly inhibited by the prostaglandins in picomolar to nanomolar concentrations. Misoprostol and PGE2 at concentrations of 5-50 nmol/L significantly inhibited histamine release from peritoneal mast cells stimulated with ionophore but did not affect histamine release stimulated by antigen.


CONCLUSIONS
These results show potent inhibitory effects of prostaglandins on the release of pro-ulcerogenic inflammatory mediators from mast cells. Such effects may contribute to the protective and anti-inflammatory effects of prostaglandins in the gastrointestinal tract and elsewhere.
Hogaboam
C M
CM
Gastrointestinal and Immunological Sciences Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
Bissonnette
E Y
EY
Chin
B C
BC
Befus
A D
AD
Wallace
J L
JL
D000818:Animals; D002478:Cells, Cultured; D006636:Histamine Release / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000166:cytology; D010972:Platelet Activating Factor / Q000378:metabolism*; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D010972:Platelet Activating Factor; D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha