Impaired M3 and enhanced M2 muscarinic receptor contractile function in a streptozotocin model of mouse diabetic urinary bladder.
Impaired M3 and enhanced M2 muscarinic receptor contractile function in a streptozotocin model of mouse diabetic urinary bladder.
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DOI：
10.1007/s00210-010-0509-6
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发表时间：
2010-05
影响因子：
3.6
通讯作者：
Ehlert, F. J.
中科院分区：
文献类型：
--
作者：
Pak, K. J.;Ostrom, R. S.;Matsui, M.;Ehlert, F. J.
我们研究了M2和M3毒蕈碱受体在链脲佐菌素处理的小鼠膀胱中的收缩作用。在膀胱试验前2-24周，对野生型和M2毒蕈碱受体敲除（M2 KO）小鼠单次注射溶媒或链脲佐菌素（125 mg kg-1）。毛喉素对毒蕈碱激动剂oxotremorine-M引起的收缩的影响在离体膀胱（完整或剥脱膀胱）中测量。当收缩相对于KCl（50 mM）引起的收缩正常化时，来自溶媒处理的野生型和M2 KO小鼠的裸露膀胱对氧震颤素-M表现出相似的收缩反应。在链脲佐菌素治疗后8至9周，与野生型相比，来自M2 KO小鼠（N = 5）的膀胱中氧代震颤素-M的EC 50值增加3.1倍（N = 6; P < 0.001）。在完整膀胱中观察到类似的变化。在溶剂处理小鼠的裸露膀胱中，与野生型相比，毛喉素（5 µM）对M2 KO膀胱收缩的抑制作用更大。链脲佐菌素治疗后，这种毛喉素效应增加了1.6倍（P = 0.032）。在20- 24周的时间点，毛喉素的作用增加了1.7倍裸露以及完整的膀胱（P = 0.036，0.01，分别）。尽管链脲佐菌素治疗抑制裸露膀胱中M3受体介导的收缩，但通过增强M2收缩功能维持野生型膀胱中的毒蕈碱收缩功能。M2受体激活对抗毛喉素诱导的膀胱松弛，并且这种M2功能在链脲佐菌素治疗后增强。
We investigated the contractile roles of M2 and M3 muscarinic receptors in urinary bladder from streptozotocin-treated mice. Wild-type and M2 muscarinic receptor knockout (M2 KO) mice were given a single injection of vehicle or streptozotocin (125 mg kg−1) 2–24 weeks prior to bladder assays. The effect of forskolin on contractions elicited to the muscarinic agonist, oxotremorine-M, was measured in isolated urinary bladder (intact or denuded of urothelium). Denuded urinary bladder from vehicle-treated wild-type and M2 KO mice exhibited similar contractile responses to oxotremorine-M, when contraction was normalized relative to that elicited by KCl (50 mM). Eight to 9 weeks after streptozotocin treatment, the EC50 value of oxotremorine-M increased 3.1-fold in urinary bladder from the M2 KO mouse (N = 5) compared to wild type (N = 6; P < 0.001). Analogous changes were observed in intact bladder. In denuded urinary bladder from vehicle-treated mice, forskolin (5 µM) caused a much greater inhibition of contraction in M2 KO bladder compared to wild type. Following streptozotocin treatment, this forskolin effect increased 1.6-fold (P = 0.032). At the 20- to 24-week time point, the forskolin effect increased 1.7-fold for denuded as well as intact bladders (P = 0.036, 0.01, respectively). Although streptozotocin treatment inhibits M3 receptor-mediated contraction in denuded urinary bladder, muscarinic contractile function is maintained in wild-type bladder by enhanced M2 contractile function. M2 receptor activation opposes forskolin-induced relaxation of the urinary bladder, and this M2 function is enhanced following streptozotocin treatment.
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影响因子：
3.6
作者：
Griffin, Michael T.;Matsui, Minoru;Ostrom, Rennolds S.;Ehlert, Frederick J.
通讯作者：
Ehlert, Frederick J.
DOI：
10.1152/ajpregu.00009.2003
发表时间：
2003-09-01
影响因子：
2.8
作者：
Braverman, AS;Ruggieri, MR
通讯作者：
Ruggieri, MR
影响因子：
--
作者：
INOUE, R;ISENBERG, G
通讯作者：
ISENBERG, G
影响因子：
6.1
作者：
Bschleipfer, Thomas;Schukowski, Konstantin;Lips, Katrin S.
通讯作者：
Lips, Katrin S.
DOI：
10.1152/ajpregu.1998.275.5.r1654
发表时间：
1998-11-01
影响因子：
2.8
作者：
Braverman, AS;Luthin, GR;Ruggieri, MR
通讯作者：
Ruggieri, MR