Stimulated calcium entry and constitutive RhoA kinase activity cause stretch-induced detrusor contraction.
Stimulated calcium entry and constitutive RhoA kinase activity cause stretch-induced detrusor contraction.
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DOI：
10.1016/j.ejphar.2008.09.045
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发表时间：
2008-12-03
影响因子：
5
通讯作者：
Ratz PH
中科院分区：
文献类型：
--
作者：
Poley RN;Dosier CR;Speich JE;Miner AS;Ratz PH
膀胱壁肌肉(即逼尿肌平滑肌)对快速拉伸的反应是收缩的，但这种反应既不完全表征，也不完全在亚细胞水平上被理解。将兔DSM条快速拉伸(5ms)，等长保持10 S，测量最大快速拉伸收缩反应(PqsR)。检测选择性钙通道阻滞剂和激酶抑制剂改变PqsR的能力，并记录肌球蛋白轻链(MLC)和肌球蛋白磷酸酶靶向调节亚基(MYPT1)的磷酸化水平。帝斯曼对快速牵拉的反应为双相反应，包括初始收缩峰值为0.24±0.02，是KCl1诱发的最大收缩(Fo)的1.48±0.17倍S(PqsR)，然后降至较弱的补药(10 S)水平(0.12±0.03倍Fo)。PqsR依赖于肌肉拉伸的速度和程度，表现为不应期，并在M受体刺激下转换为持续反应。硝苯地平、2-氨基乙氧基二苯基硼酸酯、100μM Gd和Y-27632对PqsR有抑制作用，而阿托品、10μM Gd、LOE-908、环匹亚硝酸和GF-109203X对PqsR无抑制作用。Y-27632和硝苯地平可阻断快速牵张引起的巨噬细胞磷酸化的增加。Y-27632，但不是硝苯地平，抑制了基础水平的MYPT1的磷酸化，快速拉伸未能增加该RhoA激酶(ROCK)底物高于基础水平的磷酸化。这些数据支持这一假说，即快速拉伸需要结构性岩石活动来激活钙离子进入，并导致DSM的肌源性收缩。
Urinary bladder wall muscle (i.e., detrusor smooth muscle; DSM) contracts in response to a quick-stretch, but this response is neither fully characterized, nor completely understood at the subcellular level. Strips of rabbit DSM were quick-stretched (5 ms) and held isometric for 10 s to measure the resulting peak quick-stretch contractile response (PQSR). The ability of selective Ca2+ channel blockers and kinase inhibitors to alter the PQSR was measured, and the phosphorylation levels of myosin light chain (MLC) and myosin phosphatase targeting regulatory subunit (MYPT1) were recorded. DSM responded to a quick-stretch with a biphasic response consisting of an initial contraction peaking at 0.24 ± 0.02-fold the maximum KCl-induced contraction (Fo) by 1.48 ± 0.17 s (PQSR) before falling to a weaker tonic (10 s) level (0.12 ± 0.03-fold Fo). The PQSR was dependent on the rate and degree of muscle stretch, displayed a refractory period, and was converted to a sustained response in the presence of muscarinic receptor stimulation. The PQSR was inhibited by nifedipine, 2-aminoethoxydiphenyl borate (2-APB), 100 μM gadolinium and Y-27632, but not by atropine, 10 μM gadolinium, LOE-908, cyclopiazonic acid, or GF-109203X. Y-27632 and nifedipine abolished the increase in MLC phosphorylation induced by a quick-stretch. Y-27632, but not nifedipine, inhibited basal MYPT1 phosphorylation, and a quick-stretch failed to increase phosphorylation of this rhoA kinase (ROCK) substrate above the basal level. These data support the hypothesis that constitutive ROCK activity is required for a quick-stretch to activate Ca2+ entry and cause a myogenic contraction of DSM.
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拉伸诱导的平滑肌钙释放。
DOI：
10.1085/jgp.20028514
发表时间：
2002-06
期刊：
The Journal of general physiology
影响因子：
--
作者：
Ji G;Barsotti RJ;Feldman ME;Kotlikoff MI
通讯作者：
Kotlikoff MI
DOI：
10.1124/jpet.106.112045
发表时间：
2006-12-01
影响因子：
3.5
作者：
Bai, Donglin;del Corsso, Cristiane;Spray, David C.
通讯作者：
Spray, David C.
DOI：
10.1111/j.1464-410x.1987.tb05031.x
发表时间：
1987-12-01
期刊：
BRITISH JOURNAL OF UROLOGY
影响因子：
--
作者：
KINDER, RB;MUNDY, AR
通讯作者：
MUNDY, AR
影响因子：
6.6
作者：
Drake, MJ;Hedlund, P;Gillespie, JI
通讯作者：
Gillespie, JI
影响因子：
--
作者：
BURNSTOCK, G;PROSSER, CL
通讯作者：
PROSSER, CL