Strategy targeting neuropeptide receptors in the central and peripheral nervous systems in treatment of underactive bladder

靶向中枢和周围神经系统神经肽受体治疗膀胱活动不全的策略

• 批准号: 22591787
• 负责人: YOSHIYAMA Mitsuharu
• 金额: $ 2.91万
• 依托单位: University of Yamanashi
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591787/
• 关键词: 排尿障害; 膀胱; 尿道; 糖尿病; 脳下垂体アデニル酸シクラーゼ活性化ポリペプチド(PACAP); マウス; 低活動膀胱; 下部尿路障害; 脊髄; 神経ペプチド; 膀胱コンプライアンス; 排尿収縮圧; 残尿; 反射排尿; 尿意切迫感; 切迫性尿失禁; 神経障害; 下部尿路機能; 外尿道括約筋; 脊髄損傷; 末梢神経障害

Lower urinary tract function of genetically mutated mice with diabetes mellitus (DM) was evaluated and compared to that of the wild-type mice. The results suggest that in DM mice, mechanism controlling voiding in the forebrain is devoid of appropriate inhibitory function, and thus the animals present reflex micturition. DM mice at age of 30 week-old still retain voiding efficiency more than 80%, albeit moderately present underactive bladder. Intrathecal administration of PACAP-38 increased maximal voiding pressure and partially suppressed external urethral sphincter activity, suggesting the possibility that stimulation of spinal PACAP receptors enhancesbladder contractility and ameliorates efficiency for voiding.

对糖尿病基因突变小鼠的下尿路功能进行了检测，并与野生型小鼠进行了比较。结果提示，糖尿病小鼠前脑排尿控制机制缺乏相应的抑制功能，表现为反射性排尿。30周龄的糖尿病小鼠仍保持80%以上的排尿效率，尽管存在中度的膀胱活动不足。鞘内注射PACAP-38可增加最大排尿压，部分抑制外括约肌活动，提示刺激脊髓PACAP受体可增强膀胱收缩功能，改善排尿效率。

项目成果

Blockade of neural transmission via metabotropic glutamate receptor subtype 5 facilitates urine storage without impairing bladder contractility and micturition in mice(Abstract No. 133)

通过代谢型谷氨酸受体亚型 5 阻断神经传递，促进尿液储存而不损害小鼠膀胱收缩性和排尿（摘要编号 133）

• 发表时间: 2012
• 作者: Yoshiyama M;Tsuchiya S;Takeda M.
• 通讯作者: Takeda M.

Gene expression patterns of acid-sensing ion channels(ASICs)families in mammalian bladder.

哺乳动物膀胱中酸敏感离子通道（ASIC）家族的基因表达模式。

• 发表时间: 2010
• 作者: Kobayashi H;et al.
• 通讯作者: et al.

Intravesical infusion of a non-amiloride blocker of acid-sensing ion channels fails to affect lower urinary tract activity in unanesthetized decerebrate mice

膀胱内输注酸敏感离子通道的非阿米洛利阻断剂不能影响未麻醉去大脑小鼠的下尿路活动

• 发表时间: 2010
• 作者: Yoshiyama M;Araki I;Kobayashi H;Zakoji H;Takeda M.
• 通讯作者: Takeda M.

Hypertension and type 2 diabetes mellitus are highly associated with nocturia than metabolic syndrome in Japanese population.

在日本人群中，高血压和 2 型糖尿病与夜尿症的相关性高于代谢综合征。

• 发表时间: 2010
• 作者: Imamura N;Nakagomi H;Yoda Y;Zakoji H;Kobayashi H;Tsuchida T;Fukazawa M;Yoshiyama M;Araki I;Takeda M.
• 通讯作者: Takeda M.

代謝型グルタミン酸受容体サブタイプ5を介する神経伝達の遮断は膀胱収縮性及び排尿を損ねずに蓄尿を促す

通过代谢型谷氨酸受体亚型 5 阻断神经传递可促进尿液收集，而不损害膀胱收缩性和排尿。

• 发表时间: 2012
• 作者: 芳山充晴;土屋幸子;望月勉;中込宙史;宮本達也;吉良聡;武田正之
• 通讯作者: 武田正之