Pharmacological and molecular evidence for kinin B 1 receptor expression in urinary bladder of cyclophosphamide‐treated rats

In the present study, we developed an experimental model of cystitis induced by cyclophosphamide (CYP). In order to characterize des‐Arg 9 ‐BK‐induced contraction on the urinary bladder (UB) during the development of inflammation and to quantify kinin B 1 receptor gene expression using a quantitative RT–PCR technique. In the presence of peptidase inhibitors captopril (10 μ M ), DL ‐thiorphan (1 μ M ) and DL‐2‐mercaptomethyl‐3‐guanidino‐ethylthiopropanoic acid (MERGEPTA 5 μ M ), bradykinin (BK) (0.3–3,000 n M ) evoked a concentration‐dependent contraction of rat UB which was not different between the CYP‐ and vehicle‐treated groups. Unlike BK, des‐Arg 9 ‐BK (0.3–100,000 n M ) did not contract UB from vehicle‐treated rats but contracted vigorously bladder strips from CYP‐treated rats 14, 24 and 168 h after treatment. In UB of 24 h treated rat, the pD 2 value of des‐Arg 9 ‐BK was 7.3±0.1. The cyclo‐oxygenase inhibitor indomethacin (3 μ M ) reduced by 30% the maximal response of des‐Arg 9 ‐BK. Both the kinin B 1 receptor antagonists des‐Arg 9 ‐[Leu 8 ]BK (10 μ M ) and des‐Arg 10 ‐Hoe 140 (10 μ M ) produced a rightward shift of the concentration‐response curve to des‐Arg 9 ‐BK yielding pK B values of 6.8±0.2 and 7.2±0.1, respectively, whilst the kinin B 2 receptor antagonist Hoe 140 (1 μ M ) had no effect. After CYP treatment, mRNA coding for the kinin B 1 receptor appeared predominantly in UB. In this organ, the induction was progressive, reaching a maximum 48 h after CYP treatment. In conclusion, the present study provides strong evidence for an induction of kinin B 1 receptors in UB of CYP‐treated rats. This was associated at a molecular level with an increase in mRNA expression of the gene coding for the kinin B 1 receptor. This kinin receptor displayed the whole features of a classical rat kinin B 1 receptor.British Journal of Pharmacology (1999) 128 , 213–219; doi: 10.1038/sj.bjp.0702769