Stimulation of prostaglandin production in rabbit ileal mucosa by bradykinin

Abstract

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.