Int Neurourol J.  2015 Mar;19(1):12-18. 10.5213/inj.2015.19.1.12.

Role of Nicotinic Acetylcholine Receptor alpha3 and alpha7 Subunits in Detrusor Overactivity Induced by Partial Bladder Outlet Obstruction in Rats

• Kim HS
• Park WJ
• Park EY
• Koh JS
• Hwang TK
• Kim JC

• KMID: 2380821
• DOI: http://doi.org/10.5213/inj.2015.19.1.12

Abstract

PURPOSE
To investigate the role of alpha3 and alpha7 nicotinic acetylcholine receptor subunits (nAChRs) in the bladder, using a rat model with detrusor overactivity induced by partial bladder outlet obstruction (BOO).
METHODS
Forty Sprague-Dawley rats were used: 10 were sham-operated (control group) and 30 were observed for 3 weeks after partial BOO. BOO-induced rats were further divided into 3 groups: Two groups of 10 rats each received intravesicular infusions with hexamethonium (HM group; n=10) or methyllycaconitine (MLC group; n=10), which are antagonists for alpha3 and alpha7 nAChRs, respectively. The remaining BOO-induced rats received only saline infusion (BOO group; n=10). Based on the contraction interval measurements using cystometrogram, the contraction pressure and nonvoiding bladder contractions were compared between the control and the three BOO-induced groups. Immunofluorescent staining and Western blotting were used to analyze alpha3 and alpha7 nAChRs levels.
RESULTS
The contraction interval of the MLC group was higher than that of the BOO group (P<0.05). Nonvoiding bladder contraction almost disappeared in the HM and MLC groups. Contraction pressure increased in the BOO group (P<0.05) compared with the control group and decreased in the HM and MLC groups compared with the BOO group (P<0.05). Immunofluorescence staining showed that the alpha3 nAChR signals increased in the urothelium, and the alpha7 nAChR signals increased in the urothelium and detrusor muscle of the BOO group compared with the control group. Western blot analysis showed that both alpha3 and alpha7 nAChR levels increased in the BOO group (P<0.05).
CONCLUSIONS
Alpha3 and alpha7 nAChRs are associated with detrusor overactivity induced by BOO. Furthermore, nAChR antagonists could help in clinically improving detrusor overactivity.

Keyword

Urinary Bladder, Overactive; Alpha7 Nicotinic Acetylcholine Receptor; Urinary Bladder Neck Obstruction

MeSH Terms

alpha7 Nicotinic Acetylcholine Receptor
Animals
Blotting, Western
Fluorescent Antibody Technique
Hexamethonium
Models, Animal
Rats*
Rats, Sprague-Dawley
Receptors, Nicotinic*
Urinary Bladder
Urinary Bladder Neck Obstruction*
Urinary Bladder, Overactive
Urothelium
Hexamethonium
Receptors, Nicotinic