Stimulation of prostaglandin production in rabbit ileal mucosa by bradykinin

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 226; no. 3; pp. 749 - 755
• Main Authors: HOJVAT, S. A, MUSCH, M. W, MILLER, R. J
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.09.1983
• Subjects: Animals; Arachidonic Acid; Arachidonic Acids - metabolism; Biological and medical sciences; Bradykinin - pharmacology; Calcimycin - pharmacology; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Dinoprostone; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Ileum; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestine. Mesentery; Kallidin - pharmacology; Male; Melitten - pharmacology; Phospholipases - antagonists & inhibitors; Prostaglandin Antagonists - pharmacology; Prostaglandins - biosynthesis; Prostaglandins E - metabolism; Rabbits; Vertebrates: digestive system; Small intestine
• ISSN: 0022-3565; 1521-0103

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.