Bschleipfer_2012_Life.Sci_91_1077

AIMS: In patients with bladder outlet obstruction (BOO), dysregulation of bladder afferent neurons seems to contribute to irritative symptoms. Cholinergic receptors, addressed by both neuronal and non-neuronal (urothelial) acetylcholine, can alter neuronal excitability. Thus we investigated the influence of BOO on the expression of muscarinic (mAChR) and nicotinic (nAChR) acetylcholine receptors in the lumbosacral dorsal root ganglia (DRG) of mice. MAIN
METHODS: BOO was induced in 13 C57/BL6 mice by partial suturing of the urethra. Eleven mice were sham-operated (loose/freely movable suture around the urethra), and eleven untreated mice served as controls. Cystometry was performed five weeks later in conscious mice. DRG at segmental levels L5-S2 were dissected and real-time quantitative PCR was performed. Expression of mAChR subtypes M1-M5 and nAChR subunits alpha2-7, alpha9-10, beta2-4 was examined. KEY FINDINGS: Expression of all mAChR subtypes and nAChR subunits alpha3-7, alpha10, beta2-4 was detected. Expression of alpha2 and alpha9 was absent. Rank order of expression was M2>M4>M3>M5>M1, alpha3>/=alpha6>alpha7>alpha4>alpha10>alpha5 and beta2>beta4>beta3 in untreated animals. BOO mice presented distinct obstruction with development of residual urine. Sham mice showed only minimal BOO. Relative mRNA expression of nAChR subunits revealed significant reduction of alpha3, alpha5, alpha6, alpha10 and beta4 in sham-operated vs. untreated mice. In BOO vs. sham-operated mice, reduction of nAChR subunits alpha10 (p=0.038) and alpha5 (p=0.053) was found. SIGNIFICANCE: BOO has a considerable impact on nAChR, but not on mAChR mRNA expression in sensory neurons. We hypothesize that a reduction in mRNA expression of nAChR subunits represents a link to altered sensitivity under non-obstructive conditions.