RESPONSE OF THE ISOLATED GUINEA-PIG BLADDER TO EXOGENOUS AND ENDOGENOUS LEUKOTRIENES

Noninfectious urinary bladder inflammation is a poorly understood phenomenon, and the participation of leukotrienes (LTs) in the pathogenesis of bladder inflammation is unclear. Leukotrienes are synthesized by the bladder, and exogenous LTs induce contraction of isolated bladder segments. LTD4 and LTC4 were more potent contractile agents than LTE4. Leukotriene-induced contractions were blocked by ICI 198,615 (10(-6) M. and 10(-7) M.) a specific LT receptor antagonist. In the presence of indomethacin (5 x 10(-6) M.), bladder contraction in response to LTD(4) was increased. Endogenous LT release was studied using an experimental model of cystitis. Antigen (ovalbumin 10(-6) to 10(-2) mg./ml.) challenge of bladder segments isolated from actively sensitized animals induced release of LT, prostaglandin D-2, and histamine. A-64077 (Zileuton), a 5-lipoxygenase (5-LO) inhibitor, significantly reduced contraction of sensitized bladder tissue in response to antigen challenge in a concentration-dependent manner and abolished LT release. These data indicate that the guinea pig urinary bladder produces sulfidopeptide-LTs that can be released upon specific stimulation. Furthermore, LTs activate specific receptors promoting bladder contraction. Our findings suggest that specific 5-LO inhibitors or LT-receptor antagonists might be useful in treating or preventing bladder inflammation.