Characterization of kinin receptors in human cultured detrusor smooth muscle cells

F. Bellucci, P. Cucchi, P. Santicioli, M. Lazzeri, D. Turini, S. Meini

Research output: Contribution to journalArticlepeer-review

Abstract

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. B 1 and B 2 kinin receptors were characterized by means of radioligand and functional experiments (PI accumulation and PGE 2 release).Key results:[ 3H]-[desArg 9]-Lys-BK and [ 3H]-BK saturation studies indicated receptor density (B max) and K d values of 19 or 113 fmol mg -1, and 0.16 or 0.11 nM for the B 1 or B 2 receptors, respectively. Inhibition binding studies indicated the selectivity of the B 1 receptor antagonist [desArg 9Leu 8]-Lys-BK and of the B 2 receptor antagonists Icatibant and MEN16132. [DesArg 9]-Lys-BK and BK induced PI accumulation with an EC 50 of 1.6 and 1.4 nM and different maximal responses (E max of [desArg 9]-Lys-BK was 10% of BK). BK also induced prostaglandin E 2 release (EC 50 2.3 nM), whereas no response was detected with the B 1 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 B 1 than for the B 2 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.

Original languageEnglish
Pages (from-to)192-199
Number of pages8
JournalBritish Journal of Pharmacology
Volume150
Issue number2
DOIs
Publication statusPublished - Jan 2007

Keywords

  • Human urinary bladder
  • Icatibant
  • Interleukin-1β
  • MEN16132
  • PLC activation
  • Tumour necrosis factor-α
  • Upregulation

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Characterization of kinin receptors in human cultured detrusor smooth muscle cells'. Together they form a unique fingerprint.

Cite this