BRADYKININ-INDUCED RESPONSES IN A COAXIAL BIOASSAY SYSTEM COMPOSED OFRAT ANOCOCCYGEUS MUSCLE AND GUINEA-PIG TRACHEA

1. Epithelium-dependent effects of bradykinin (BK) were investigated i n a coaxial bio-assay system which consisted of guinea pig trachea as donor organ and rat anococcygeus muscle as test tissue. 2. BK (10(-9) to 10(-5) M) produced concentration-dependent relaxations on the pheny lephrine (3x10(-6) M) precontracted rat anococcygeus muscle mounted al one, Relaxations decreased significantly when muscle was mounted in ep ithelium-intact trachea. There was also a significant difference betwe en the relaxations obtained in the muscle within epithelium-intact and epithelium denuded trachea (at 10(-7) to 10(-5) M concentrations). 3. Capsaicin (10(-5) M) pretreatment did not change BK (10(-9) to 10(-5) M)-induced relaxations in each preparation compared with vehicle pret reatment. Indomethacin (10(-6) M) in combination with thiorphan (10(-5 ) M) and atropine (10(-6) M) did not affect the BK-induced relaxations of the muscle within capsaicin-pretreated epithelium intact or denude d trachea. 4. CGS 8515 (a specific 5-lipoxygenase inhibitor, 10(-6) M) did not change BK (10(-5) M)-induced relaxation on the muscle alone, and caused an increase of BK-induced relaxation on the muscle within e pithelium-intact trachea compared with that obtained without CGS 8515. 5. Results showed that epithelial or nonepithelial factors were capab le of modulating the responsiveness of rat anococcygeus muscle to BK. The decreased relaxation by BK in anococcygeus muscle did not occur by the release of cyclooxygenase products or tachykinins from tracheal e pithelium, but it may have occurred by the contractile action of lipox ygenase product secreted by nonepithelial sources. In addition, BK mig ht stimulate the secretion of an epithelium-derived inhibitory factor from the trachea. (C) 1998 Elsevier Science Inc.