P2Y(6)-deficiency increases micturition frequency and attenuates sustained contractility of the urinary bladder in mice.

P2Y(6)-deficiency increases micturition frequency and attenuates sustained contractility of the urinary bladder in mice.
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DOI:
10.1038/s41598-017-00824-2
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发表时间:
2017-04-10
期刊:
影响因子:
4.6
通讯作者:
Koizumi S
Koizumi S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kira S;Yoshiyama M;Tsuchiya S;Shigetomi E;Miyamoto T;Nakagomi H;Shibata K;Mochizuki T;Takeda M;Koizumi S

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P2 Y 6受体在膀胱功能中的作用最近在下尿路研究中引起了大量关注。我们通过比较P2 Y 6缺陷小鼠和野生型小鼠,进行了这项研究,以确定P2 Y 6受体在正常表型下尿路功能中的作用。在体内实验中,与野生型小鼠相比,P2 Y 6缺陷型小鼠排尿更频繁,膀胱容量更小;然而,在去大脑、未麻醉条件下的膀胱测压期间,这些组之间的膀胱充盈压力/体积关系没有差异。体内膀胱收缩的分析揭示了两组之间的显著差异,P2 Y 6缺陷小鼠呈现出明显更短的膀胱收缩持续时间,但峰值收缩压力没有差异。然而,在体外实验的分析表明,没有P2 Y 6参与收缩和舒张膀胱肌条和ATP释放的原代培养的尿路上皮细胞的机械刺激。这些结果表明,P2 Y 6受体在中枢神经系统,背根神经节,或两者都参与抑制膀胱传入信号或敏感性在脑桥排尿中心和逼尿肌中的受体可能涉及促进维持膀胱收缩力。
The role of the P2Y6 receptor in bladder function has recently attracted a great deal of attention in lower urinary tract research. We conducted this study to determine contributions of the P2Y6 receptor in lower urinary tract function of normal phenotypes by comparing P2Y6-deficient mice and wild-type mice. In in vivo experiments, P2Y6-deficient mice had more frequent micturition with smaller bladder capacity compared to wild-type mice; however, there was no difference between these groups in bladder-filling pressure/volume relationships during cystometry under decerebrate, unanaesthetized conditions. Analysis of in vivo bladder contraction revealed significant difference between the 2 groups, with P2Y6-deficient mice presenting markedly shorter bladder contraction duration but no difference in peak contraction pressure. However, analysis of in vitro experiments showed no P2Y6 involvements in contraction and relaxation of bladder muscle strips and in ATP release by mechanical stimulation of primary-cultured urothelial cells. These results suggest that the P2Y6 receptor in the central nervous system, dorsal root ganglion, or both is involved in inhibition of bladder afferent signalling or sensitivity in the pontine micturition centre and that the receptor in the detrusor may be implicated in facilitation to sustain bladder contraction force.