Bradykinin stimulates prostaglandin E2 production and cyclooxygenase activity in equine nonglandular and glandular gastric mucosa in vitro.
BACKGROUND
There are few data available regarding regulation of prostaglandin (PG) generation by equine gastric mucosae and the role of the cyclooxygenase (COX) isoforms in their production.


OBJECTIVE
To: 1) characterise and quantify PGE2 output in vitro; 2) examine the sensitivity of PGE2 production to exogenous bradykinin (BK) exposure; 3) determine the contribution of the COX-1 and COX-2 pathways to basal and BK-stimulated PGE2 production; and 4) measure if BK influences electrogenic ion transport in equine gastric mucosae in vitro.


METHODS
Full thickness gastric sheets were obtained from horses at post mortem, stripped of muscle layers and mounted in Ussing chambers. Tissues were exposed to bradykinin (BK, 0.1 micromol/l) either alone, or following pretreatment with a selective COX-2 inhibitor (NS-398, 1 micromol/l) or a nonselective COX inhibitor (piroxicam, 1 micromol/l), or were untreated.


RESULTS
BK administration increased PGE2 output from the basolateral but not the apical faces of both tissue types. Piroxicam, but not NS-398, reduced basolateral PGE2 release below control levels in both tissue types. Both piroxicam and NS-398 pretreatment inhibited BK-stimulated PGE2 release. In separate experiments, BK was without effect upon electrophysiological parameters of tissues mounted in Ussing chambers.


CONCLUSIONS
PGE2 is produced by the nonglandular and glandular equine gastric mucosae in vitro. Significantly more PGE2 is released basolaterally than apically. BK stimulated the production of PGE2 from the basolateral side of both tissue types. These findings suggest that COX-1 is a significant pathway for basal PGE2 production from the basolateral faces of both nonglandular and glandular equine gastric mucosae in vitro.
Morrissey
N K
NK
University of Limerick, Limerick, Ireland.
Bellenger
C R
CR
Baird
A W
AW
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology / Q000378:metabolism*; D006736:Horses; D007527:Isoenzymes; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism*; D046509:Tissue Culture Techniques / Q000662:veterinary; D014665:Vasodilator Agents / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D007527:Isoenzymes; D014665:Vasodilator Agents; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D001920:Bradykinin