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.


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).


CONCLUSIONS
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.
Templeman
L
L
Department of Biomedical Science, University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK.
Sellers
D J
DJ
Chapple
C R
CR
Rosario
D J
DJ
Hay
D P W
DP
Chess-Williams
R
R
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects; D015288:Neurokinin A / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013552:Swine; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*
D001549:Benzamides; D010880:Piperidines; D011804:Quinolines; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; C106716:SB 223412; C073839:SR 48968; D015288:Neurokinin A