Lipopolysaccharide (LPS) Upregulates Bradykinin 1 (BK1) receptors in the isolated mouse bladder

BK1 receptors have been shown to be upregulated at sites of inflammation. The purpose of this study was to determine the effect of LPS on BK1 receptor modulation in the isolated mouse bladder. Balb/c mice were sacrificed by pentobarbital overdose, the urinary bladder removed and suspended as ring segment in tissue baths under an initial tension of 1 g. Tissues were allowed to equilibrate for 1 hour. Following equilibration, tissues were exposed to cumulative concentrations of BK, a BK2 agonist, or des-Arg9-BK (DABK), a BK1 agonist. Tissues were then washed with fresh buffer for 30 min and incubated with 100 μg/ml LPS or saline for 1 hour. After this incubation, a second concentration-response curve to the same agonist was obtained. The effect of 10 μM des-Arg9-[Leu8]-BK, a BK1 receptor antagonist, was also evaluated. BK but not DABK was found to be a potent agonist of the mouse bladder. However, both the sensitivity (measured at effective-concentration 10%; EC10) and maximal responses to DABK increased during a second exposure to the agonist. Pre-incubation of tissues with LPS increased both the maximum response and the sensitivity of tissues to DABK. LPS induced a 282-fold leftward shift in the EC10 and a 5-fold increase in maximal responses to DABK. Treatment of tissues with a BK1 receptor antagonist, 1 hour prior to LPS, abolished the increase of both maximal response and sensitivity. These results indicate that in the mouse bladder, BK1 receptors can be upregulated and that LPS potentiates this response.

Duke Scholars

Author Timothy Grant Hammond Medicine, Nephrology