LIPOPOLYSACCHARIDE UPREGULATES BRADYKININ 1 RECEPTORS IN THE ISOLATED MOUSE BLADDER

Abstract

Purpose Bradykinin 1 (B1) receptors have been shown to be upregulated at sites of inflammation. The purpose of this study was to determine the effect of lipopolysaccharide (LPS) on B1 receptor modulation in the isolated mouse bladder. Materials and Methods The contractile responses of isolated mouse bladder to B1 and B2 agonists were determined in vitro following prolonged incubation with LPS or saline. Results Bradykinin (BK), a B2 agonist, but not des-Arg 9-bradykinin (DABK), a B1 agonist, was found to be a potent contractile agonist of the mouse urinary bladder under basal conditions. However, both sensitivity and maximal response to DABK increased during a second exposure to the agonist in a time-dependent manner. In vivo or in vitro treatment with LPS increased both sensitivity and maximal response of isolated bladders to DABK, whereas bladder contraction to BK and other peptides remained the same. Treatment of tissues with a B1 receptor antagonist 45 minutes prior to second exposure to DABK, or the prostaglandin synthesis inhibitor, indomethacin, 30 minutes prior to LPS or saline incubation, significantly inhibited the increase of both maximal response and sensitivity. Conclusions These results indicate that bladder B1 receptors can be upregulated by LPS, and that prostaglandins seem to mediate the effects of the B1 receptor activation in the isolated mouse bladder.