Evaluation of the role of neurolinins and urecholine hypersensitivity in an animal model of infravesical outflow obstruction.
OBJECTIVE
To determine whether detrusor muscle strips from a male rat with infravesical outflow obstruction model demonstrate supersensitivity to parasympathomimetic and neurokinin NK-1 and NK-2 selective agonists.


METHODS
Bladder instability developed after 6 weeks of partial urethral obstruction. The micturition frequency and voided volume were determined in unanesthetized animals. Detrusor hypertrophy was confirmed by evaluation of bladder weight. In vitro organ bath was used to compare the affinity and maximal activity of bethanechol and neurokinin NK-1 and NK-2 selective agonists on strips from the detrusor muscle of sham and obstructed rats. Bethanechol, N-Ac[Arg6, Sar9, Met(O2)]-SP(6-11), and [beta-Ala8]-NKA(4-10) were used to characterize cholinergic muscarinic, neurokinin NK-1 and NK-2 receptors. Results. No significant differences in affinities and maximal responses were found using 10-mg detrusor muscle strips with each of the three agonists.


CONCLUSIONS
Bladder instability produced by outlet obstruction does not involve changes in the affinity or maximal activity of cholinergic muscarinic, neurokinin NK-1 and NK-2 receptors. Furthermore, detrusor supersensitivity to neurokinins or bethanechol was not seen. This suggests that bladder instability is not due to an increased affinity or maximal response to neurokinins or parasympathomimetics.
Dion
S B
SB
Urology Research Laboratories, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Québec, Canada.
Zvara
P
P
Tu
L M
LM
Richer
M
M
Corcos
J
J
D000818:Animals; D001626:Bethanechol Compounds / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth; D015287:Neurokinin B / Q000819:agonists*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000187:drug effects*; D018041:Receptors, Neurokinin-2 / Q000187:drug effects*; D014524:Urethral Obstruction / Q000503:physiopathology*
D001626:Bethanechol Compounds; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D015287:Neurokinin B