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Background and purpose: Kinins have an important role in inflammatory cystitis and in animal pathophysiological models, by acting on epithelium, fibroblasts, sensory innervation and smooth muscle. The aim of this study was to characterize the receptors responsible for direct motor responses induced by kinins on human detrusor. Experimental approach: Human detrusor cells from biopsies were isolated and mantained in culture. B1 and B2 kinin receptors were characterized by means of radioligand and functional experiments (PI accumulation and PGE2 release). Key results: [3H]-[desArg9]-Lys-BK and [3H]-BK saturation studies indicated receptor density (Bmax) and Kd values of 19 or 113 fmol mg−1, and 0.16 or 0.11 nM for the B1 or B2 receptors, respectively. Inhibition binding studies indicated the selectivity of the B1 receptor antagonist [desArg9Leu8]-Lys-BK and of the B2 receptor antagonists Icatibant and MEN16132. [DesArg9]-Lys-BK and BK induced PI accumulation with an EC50 of 1.6 and 1.4 nM and different maximal responses (Emax of [desArg9]-Lys-BK was 10% of BK). BK also induced prostaglandin E2 release (EC50 2.3 nM), whereas no response was detected with the B1 receptor agonist. The incubation of detrusor smooth muscle cells with interleukin 1β (IL-1β) or tumour necrosis factor-α (TNF-α) (10 ng ml−1) induced a time-dependent increase in radioligand-specific binding, which was greater for the B1 than for the B2 receptor. Conclusions and Implications: Human detrusor smooth muscle cells in culture retain kinin receptors, and represent a suitable model to investigate the mechanisms and changes that occur under chronic inflammatory conditions. British Journal of Pharmacology (2007) 150, 192–199. doi:10.1038/sj.bjp.0706976 |
