Laboratory for Development Pharmacology, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, Izunokuni-shi, Shizuoka, Japan.
Am J Physiol Renal Physiol. 2013 Apr 1;304(7):F1020-7. doi: 10.1152/ajprenal.00365.2012. Epub 2013 Jan 23.
We investigated the effects of partial bladder outlet obstruction (BOO) on the function and gene expression of 5-hydroxytryptamine (5-HT) receptor subtypes in rat bladder. Isometric contractions of the isolated bladders from sham-operated control and BOO rats were examined. The contractile responses to 5-HT were significantly increased in BOO rat bladder strips, while the responses to KCl, carbachol, or phenylephrine were not different from the control. The 5-HT-induced hypercontraction in BOO rat bladder strips was inhibited by ketanserin, a 5-HT(2A) receptor antagonist. The contractile responses to 5-HT in bladder strips were not affected by urothelium removal from the intact bladder. The gene expression of 5-HT receptor subtypes in the bladders was analyzed by RT-PCR. The mRNA expression of the 5-HT(2A), 5-HT(2B), 5-HT(2C), 5-HT(4), and 5-HT(7) receptors was detected in both the control and BOO rat bladders. Quantitative RT-PCR analysis showed there was a significant increase of 5-HT(2A) receptor mRNA in the BOO rat bladder compared with the control bladder. On the other hand, the gene expression of the 5-HT(4) receptor was not changed in the BOO rat bladder. These results suggest that the increased contractile responses to 5-HT in BOO rat bladder may be partly caused by 5-HT(2A) receptor upregulation in the detrusor smooth muscles.
我们研究了部分膀胱出口梗阻(BOO)对大鼠膀胱 5-羟色胺(5-HT)受体亚型功能和基因表达的影响。检查了假手术对照和 BOO 大鼠分离膀胱的等长收缩。与对照组相比,BOO 大鼠膀胱条带对 5-HT 的收缩反应明显增加,而对 KCl、卡巴胆碱或苯肾上腺素的反应没有差异。5-HT(2A)受体拮抗剂酮色林抑制 BOO 大鼠膀胱条带中 5-HT 诱导的过度收缩。完整膀胱的尿路上皮去除对膀胱条带中 5-HT 诱导的收缩反应没有影响。通过 RT-PCR 分析膀胱中 5-HT 受体亚型的基因表达。在对照和 BOO 大鼠膀胱中均检测到 5-HT(2A)、5-HT(2B)、5-HT(2C)、5-HT(4)和 5-HT(7)受体的 mRNA 表达。定量 RT-PCR 分析显示,与对照组相比,BOO 大鼠膀胱中 5-HT(2A)受体 mRNA 表达显著增加。另一方面,5-HT(4)受体的基因表达在 BOO 大鼠膀胱中没有改变。这些结果表明,BOO 大鼠膀胱中 5-HT 收缩反应的增加可能部分是由于逼尿肌平滑肌中 5-HT(2A)受体的上调所致。