Bladder outlet obstruction influences mRNA expression of cholinergic receptors on sensory neurons in mice

作者：Bschleipfer Thomas^*; Nandigama Rajender; Moeller Stefan; Illig Christian; Weidner Wolfgang; Kummer Wolfgang

来源：Life Sciences, 2012, 91(21-22): 1077-1081.

DOI：10.1016/j.lfs.2012.05.007

• Bladder outlet obstruction
• Cholinergic receptors
• Real-time RT-PCR
• Sensory neurons

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. %26lt;br%26gt;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 alpha 2-7, alpha 9-10, beta 2-4 was examined. %26lt;br%26gt;Key findings: Expression of all mAChR subtypes and nAChR subunits alpha 3-7, alpha 10, beta 2-4 was detected. Expression of alpha 2 and alpha 9 was absent Rank order of expression was M2 %26gt; M4 %26gt; M3 %26gt; M5 %26gt; M1, alpha 3 %26gt;= alpha 6 %26gt; alpha 7 %26gt; alpha 4 %26gt; alpha 10 %26gt; alpha 5 and beta 2 %26gt; beta 4 %26gt; beta 3 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 alpha 3, alpha 5, alpha 6, alpha 10 and beta 4 in sham-operated vs. untreated mice. In BOO vs. sham-operated mice, reduction of nAChR subunits alpha 10 (p=0.038) and alpha 5 (p = 0.053) was found. %26lt;br%26gt;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.

• 出版日期2012-11-27