Role of the soluble guanylyl cyclase α1-subunit in mice corpus cavernosum smooth muscle relaxation
Role of the soluble guanylyl cyclase α1-subunit in mice corpus cavernosum smooth muscle relaxation
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可溶性鸟苷酸环化酶α1亚基在小鼠海绵体平滑肌松弛中的作用
DOI：
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发表时间：
2008
影响因子：
2.6
通讯作者：
J. Voorde
中科院分区：
文献类型：
--
作者：
S. Nimmegeers;P. Sips;Emmanuel S. Buys;Emmanuel S. Buys;Kelly Decaluwé;P. Brouckaert;J. Voorde
可溶性鸟苷酸环化酶（sGC）是一氧化氮（NO）的主要效应分子，因此是治疗勃起功能障碍的一个有趣的治疗靶点。为了评估sGCα1β1亚型在阴茎海绵体（CC）松弛中的功能重要性，将来自雄性sGCα1−/−和野生型小鼠的CC固定在器官浴中进行等长张力记录。在sGCα1−/− CC中，内源性NO（来自乙酰胆碱、缓激肽和电场刺激）的松弛几乎被消除。在sGCα1−/−小鼠中，外源性NO（来自硝普钠和NO气体）、BAY 41-2272（NO非依赖性sGC刺激剂）和T-1032（磷酸二酯酶5型抑制剂）的舒张作用也显著降低。sGC抑制剂1H-[1，2，4]恶二唑并[4，3-a]喹喔啉-1-酮显著降低了sGCα1−/−小鼠中观察到的剩余外源性NO诱导的舒张。通过使用毛喉素（腺苷酸环化酶激活剂）和8-pCPT-cGMP（cGMP类似物）观察到的未改变的舒张，证明了sGC相关反应受损的特异性。总之，sGCα1β1亚型参与了对NO和NO非依赖性sGC刺激剂的反应的体平滑肌松弛。外源性NO在sGCα1−/−小鼠中仍有一定作用，这一事实表明有其他途径的作用。
Soluble guanylyl cyclase (sGC) is the major effector molecule for nitric oxide (NO) and as such an interesting therapeutic target for the treatment of erectile dysfunction. To assess the functional importance of the sGCα1β1 isoform in corpus cavernosum (CC) relaxation, CC from male sGCα1−/− and wild-type mice were mounted in organ baths for isometric tension recording. The relaxation to endogenous NO (from acetylcholine, bradykinin and electrical field stimulation) was nearly abolished in the sGCα1−/− CC. In the sGCα1−/− mice, the relaxing influence of exogenous NO (from sodium nitroprusside and NO gas), BAY 41-2272 (NO-independent sGC stimulator) and T-1032 (phosphodiesterase type 5 inhibitor) were also significantly decreased. The remaining exogenous NO-induced relaxation seen in the sGCα1−/− mice was significantly decreased by the sGC-inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. The specificity of the impairment of the sGC-related responses was demonstrated by the unaltered relaxations seen with forskolin (adenylyl cyclase activator) and 8-pCPT-cGMP (cGMP analog). In conclusion, the sGCα1β1 isoform is involved in corporal smooth muscle relaxation in response to NO and NO-independent sGC stimulators. The fact that there is still some effect of exogenous NO in the sGCα1−/− mice suggests the contribution of (an) additional pathway(s).
影响因子：
158.5
作者：
DETEJADA, IS;GOLDSTEIN, I;COHEN, RA
通讯作者：
COHEN, RA
影响因子：
2.9
作者：
Peter S. T. Yuen;L. Potter;D. Garbers
通讯作者：
Peter S. T. Yuen;L. Potter;D. Garbers