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

• Published in: BJU international Vol. 92; no. 7; pp. 787 - 792
• Main Authors: Templeman, L., Sellers, D.J., Chapple, C.R., Rosario, D.J., Hay, D.P.W., Chess‐Williams, R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-11-2003; Blackwell
• Subjects: Animals; Benzamides - pharmacology; Biological and medical sciences; bladder neck; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; human detrusor; Humans; Muscle Contraction - drug effects; neurokinin A; Neurokinin A - pharmacology; pig bladder dome; Piperidines - pharmacology; Quinolines - pharmacology; Receptors, Neurokinin-2 - antagonists & inhibitors; Receptors, Neurokinin-2 - metabolism; Receptors, Neurokinin-3 - antagonists & inhibitors; Receptors, Neurokinin-3 - metabolism; Swine; Urinary Bladder - drug effects; Urinary Bladder - metabolism; Vertebrates: urinary system; Human; Peptide hormone; Hormonal mediator; Biology; pig bladder dome; Muscle contraction; human detrusor; Neurokinin A; Detrusor muscle; Bladder neck; Tachykinin receptor; Tachykinin; Biological receptor
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1046/j.1464-410X.2003.04458.x

Authors from Sheffield and the USA investigated the role of neurokinin receptors in mediating contraction of detrusor muscle strips from human and pig. They found that NK‐2 receptors subtypes mediate neurokinin A‐induced contraction of the detrusor muscle, and that the NK‐3 receptor appears not to have such a role.
Another study, from a variety of European and American centres, determined the expression and plasma membrane location of isoforms of Na,K‐ATPase in the rat ventral prostate; they were localised in the lateral and basolateral plasma membrane domain prostatic epithelial cells, and the authors draw conclusions about the significance of these findings.
Finally authors from Yale University investigated the effects of castration on the expressions of endothelins, endothelin receptors and converting enzyme‐1 in the rat seminal vesicle. Their findings led them to suggest that testosterone has a regulatory role in the expression of the endothelin receptor system in the rat seminal vesicle.
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.