Stimulation of prostaglandin production in rabbit ileal mucosa by bradykinin.
When rabbit ileal mucosa was incubated with exogenous [3H]arachidonic acid (AA), its major metabolites, identified by comigration with known standards on thin-layer chromatography, were prostaglandin (PG) E2, 6-keto-PGF1 alpha and to a lesser extent PGF2 alpha and PGD2. The rate of prostanoid release from the serosal surface of the mucosa only was increased after incubation th either bradykinin, lys-bradykinin, melittin or the calcium ionophore A 23187, in a rapid and dose-dependent fashion. Peptide concentrations as low as 10(-9) M were effective. Kinin-induced release of AA or its metabolites required the presence of Ca++ in the incubation medium. Stimulation of prostanoid release by lys-bradykinin was completely blocked by indomethacin. The combined lipoxygenase/cyclooxygenase inhibitors BW 755 and eicosa-5,8,11,14-tetraynoic acid and the lipoxygenase inhibitor nordihydroguaiaretic acid also blocked the stimulation of PG synthesis by lys-bradykinin. These inhibitors caused an increase in levels of AA released from the tissue by lys-bradykinin. The phospholipase inhibitors, mepacrine and U- 10029, inhibited the lys-bradykinin-stimulated release of both prostanoids and AA. At higher concentrations, U- 10029 inhibited the stimulation of transepithelial potential difference and short-circuit current across rabbit ileal mucosa produced by lys-bradykinin. These results support the hypothesis that bradykinin-stimulated intestinal secretion may be mediated by PGs.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D007082:Ileum; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007609:Kallidin / Q000494:pharmacology; D008297:Male; D008555:Melitten / Q000494:pharmacology; D010740:Phospholipases / Q000037:antagonists & inhibitors; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000378:metabolism; D011817:Rabbits
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011458:Prostaglandins E; D008555:Melitten; D016718:Arachidonic Acid; D007609:Kallidin; D000001:Calcimycin; D010740:Phospholipases; D015232:Dinoprostone; D001920:Bradykinin; D002118:Calcium