Michishita Mai, Yano Kazuo, Kasahara Ken-ichi, Tomita Ken-ichi, Matsuzaki Osamu
Laboratory for Pharmacology, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation.
Biomed Res. 2015;36(3):187-94. doi: 10.2220/biomedres.36.187.
Serotonin (5-hydroxytryptamine; 5-HT)-induced bladder contraction is enhanced after partial bladder outlet obstruction (pBOO) in rats. We investigated time-dependent changes in bladder contraction and expression of 5-HT(2A) and 5-HT(2B) receptor mRNA in bladder tissue to elucidate the mechanism of this enhancement. On day 3 and 7 after pBOO, contractile responses of isolated rat bladder strips to 5-HT were increased compared with that in sham-operated rats; on day 14, the response had decreased to the same level as that in sham rat bladders. In contrast, carbacholinduced contraction was not enhanced by pBOO at any time point. In sham rats, 5-HT(2A) receptor mRNA was expressed in the urothelium, and 5-HT(2B) receptor mRNA was expressed in the detrusor muscle layer. In pBOO rats, both receptor mRNAs were increased in the detrusor muscle and subserosal layers, but not in the urothelium. The increase of 5-HT(2A) receptor mRNA was maintained from day 3 to day 14 after pBOO, and 5-HT(2B) receptor mRNA was increased on day 7 after pBOO. These results suggested that pBOO induced up-regulation of the 5-HT(2A) and 5-HT(2B) receptors in the detrusor muscle and subserosal layers of the bladder, and such up-regulation may be related to the enhanced bladder contractile response to 5-HT.
在大鼠膀胱出口部分梗阻(pBOO)后,血清素(5-羟色胺;5-HT)诱导的膀胱收缩增强。我们研究了膀胱收缩以及膀胱组织中5-HT(2A)和5-HT(2B)受体mRNA表达的时间依赖性变化,以阐明这种增强的机制。在pBOO后的第3天和第7天,与假手术大鼠相比,分离的大鼠膀胱条对5-HT的收缩反应增强;在第14天,反应已降至与假手术大鼠膀胱相同的水平。相比之下,卡巴胆碱诱导的收缩在任何时间点都未因pBOO而增强。在假手术大鼠中,5-HT(2A)受体mRNA在上皮中表达,5-HT(2B)受体mRNA在逼尿肌层中表达。在pBOO大鼠中,两种受体mRNA在逼尿肌和浆膜下层中均增加,但在上皮中未增加。5-HT(2A)受体mRNA的增加在pBOO后第3天至第14天持续存在,5-HT(2B)受体mRNA在pBOO后第7天增加。这些结果表明,pBOO诱导膀胱逼尿肌和浆膜下层中5-HT(2A)和5-HT(2B)受体上调,这种上调可能与膀胱对5-HT的收缩反应增强有关。