Investigation of neurokinin-2 and -3 receptors in the human and pig bladder.

OBJECTIVE: To investigate the role of neurokinin (NK)-2 and -3 receptors in mediating the contraction of detrusor muscle strips from human and pig, to determine whether the pig is a good model for the study of tachykinin receptors in the human bladder, as the biological actions of tachykinins, e.g. substance P and NKA are mediated via three distinct receptor subtypes, NK-1, -2 and -3. MATERIALS AND METHODS: Strips of detrusor muscle were obtained from the bladder dome and neck of female pigs and from patients undergoing cystectomy. Cumulative concentration-response curves to NKA were obtained in the absence and presence of either the NK-2 receptor-selective antagonist SR48968 or the NK-3 receptor-selective antagonist SB223412. RESULTS: NKA produced concentration-dependent contractions in the human and pig detrusor muscle; the curves were shifted to the right by SR48968, with high affinity (pKB 8.9, 8.3 and 8.0 in the human, pig dome and pig neck, respectively), whereas SB223412 had a minimal effect (pKB 5.8, 5.8 and 6.3, respectively). CONCLUSION: These data confirm that the NK-2 receptor subtype mediates NKA-induced contraction of the human and pig detrusor muscle. The NK-3 receptor appears to have no role in detrusor contraction of either species. The results also provide evidence that the NK-2 receptor in human and pig are the same, and the latter may be an appropriate species to study tachykinin-induced contractions in human bladder.

Urothelium derived inhibitory factor and cross-talk among receptors in the trigone of the bladder of the pig.

PURPOSE: In the dome of the bladder of the pig muscarinic receptor stimulation has been shown to release a factor from the urothelium that exerts an inhibitory effect on the underlying smooth muscle. We examined whether the urothelium in the trigone of the bladder also releases this factor, identified which receptors stimulate its release and investigated possible cross-talk among these receptor systems in the trigone. MATERIALS AND METHODS: Paired longitudinal strips of pig bladder were isolated, the urothelium was removed from 1 strip per pair and tissues were set up in gassed Krebs solution at 37C. Cumulative concentration-response curves to carbachol, phenylephrine or histamine were constructed. In some tissues a second phenylephrine curve was constructed in the presence of 1 microM. carbachol or 1 microM. histamine. In a further group of tissues the second phenylephrine curve was constructed in the presence of 1 microM. carbachol and 1 microM. atropine or 1 microM. histamine and 100 nM. mepyramine. RESULTS: In the presence of an intact urothelium contractile responses to carbachol and histamine but not to phenylephrine were depressed. In the presence of 1 microM. carbachol or 1 microM. histamine the responses of intact urothelium strips to phenylephrine were significantly depressed. This effect was absent in the presence of atropine and mepyramine, respectively. CONCLUSIONS: Carbachol and histamine induce the release of a urothelium derived inhibitory factor in the bladder trigone. The factor appears to mediate cross-talk between these systems and the alpha-adrenoceptor system in this region of the bladder.