KINETICS OF PEPTIDE-INDUCED RELEASE OF INFLAMMATORY MEDIATORS BY THE URINARY-BLADDER

Objective To investigate the release of inflammatory mediators by the urinary bladder in response to exposure to pro-inflammatory peptides. Materials and methods Isolated guinea pig urinary bladder was incubate d with 10 mu mol/L each of substance P (SP), neurokinin A (NKA), calci tonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) , octreotide acetate (a long-acting analogue of somatostatin, SOM), or bradykinin (BK), and the release of histamine, prostaglandin (PG) E-2 , PGF(2 alpha) and leukotriene B-4 (LTB4) was determined during 0 - 5, 5 - 30 and 30 - 120 min after addition. Results Substance P, NKA, VIP and BK stimulated the release of histamine, while CGRP and SOM suppre ssed the release to below the spontaneous rates. All peptides, except CGRP and SOM, stimulated the release of PGE, between 0 and 30 min, and only VIP failed to stimulate the release of PGF(2 alpha) within 5 min of exposure. Substance P, NI(A, VIP and BI( stimulated the release of LTB4 and this required > 5 min of exposure. Conclusion These results indicate that the peptides evaluated induce an immediate and transient release of histamine and activation of cyclooxygenase and delayed act ivation of 5-lipoxygenase. These actions may directly regulate the par ticipation of these peptides in the pathogenesis of cystitis.