Molecular basis for occurence of the spontaneous activity of smooth muscle-consisting organs, and its functinal disorder.

平滑肌器官自发活动发生及其功能障碍的分子基础。

• 批准号: 08307020
• 负责人: NISHI Katsuhide
• 金额: $ 5.7万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08307020/
• 关键词: neutralizing mouse anti-c-Kit antibody; isolated gastric smooth muscle cell; sarcoplasmic reticulum; distribution of c-Kit expressing cells; Cajar's interstitial cell; colon of Hierschprung's disease patient; hunger contraction of the ileum; apamin

Nishi and his co-workers, using mouse-small intestine treated with neutralizing mouse anti-c-Kit antibody (ACK2), examined an intracellular Ca^<2+> handling mechanism in the isolated intestinal smooth muscle, and found that caffeine-induced I_<K.Caf>), carbachol-induced calcium dependent K current (I_<K.Cab>) in isolated intestinal smooth muscle cells treated with ACK2 showed altered characteristics, compared with those in the control ones, suggesting dysfunction of uptake of Ca^<2+> into the calcium storing sites Torihashi examined distribution of c-Kit expressing cells in the human intestine, their ultra structure and relation to the Cajar's interstitial cells, and found a decrease in the number of c-Kit expressing cells in the colon taken from Hirschprung's disease patients. Using ACK2 in the mouse intestine, c-Kit expressing cells were classified into groups of 1)cells not affected by treatment with ACK2, 2)cells showed developmental delay with ACK2 and 3)types of c-Kit expressing … More cells later transfomed into smooth muscle cells Katsuaki Ito examined the distribution of c-Kit expressing cells in the mouse stomach, and found that in the stomach, c-Kit expressing cells had already developed before birth, but not in the c-Kit deficient mutant mouse. Fujino et al, treated mouse with ACK2 and found that c-Kit expressing cell-deficient intestine lacking the regular pacemaker activity, showed abnormal hunger-contraction wave of the intestinal movement, suggesting dysfunction of synchronizing mechanisms of peristaltic in the intestine without pace-maker activity. Ozaki et al showed deficiency of intestinal intermuscular neural ganglia in the caudal part of the intestine in the enodotherin B receptor-deficient mutant mouse, in which hypertrophy of intestinal smooth muscle and decreased spontaneous movements of the intestine cranial to the region without the neural ganglia were observed. Yushi Ito et al examined mechanisms underlying propagating spontaneouslu occurring peristaltic in the ileum by motirin, and found that an increase in activity of calcium currents mediated through anion channels activated by a low concentration of motirin and a marked increase of anion channel activity mediated through muscarinic receptors. Takeo Ito showed that NO exerted negative control on agents-induced contraction in the rabbit cerebral median artery and the arterial smooth muscle was hyperpolarized by activation of apamin-sensitive potassium channels via an increased release of DHF induced by acetylcholine. Takahama examined afferent neural activity related to an increase of tracheal smooth muscle tone and showed that bradykinin affected afferent nerve activity and the effect was also modified by tachkinin. Less

Nishi和他的同事用中和小鼠抗c- kit抗体（ACK2）处理小鼠小肠，检测了离体肠道平滑肌细胞内Ca^<2+>处理机制，发现咖啡因诱导的I_<K。与对照组相比，经ACK2处理的离体肠平滑肌细胞中，碳水化合物诱导的钙依赖性钾电流（I_<K. cab >）表现出改变的特征，表明Ca^<2+>进入钙储存部位的摄取功能障碍，Torihashi检测了c-Kit表达细胞在人肠中的分布、它们的超结构及其与Cajar间质细胞的关系。并发现从巨噬细胞病患者身上提取的结肠中表达c-Kit的细胞数量减少。利用小鼠肠道中的ACK2，将表达c-Kit的细胞分为：1)未受ACK2影响的细胞，2)随ACK2发育迟缓的细胞和3)表达c-Kit的细胞类型。更多的细胞后来转化为平滑肌细胞，Katsuaki Ito检查了表达c-Kit的细胞在小鼠胃中的分布，发现在胃中，表达c-Kit的细胞在出生之前就已经发育。但在c-Kit缺陷突变小鼠中没有。Fujino等人用ACK2处理小鼠，发现表达c-Kit的细胞缺陷肠缺乏正常的起搏器活性，肠运动出现异常的饥饿-收缩波，提示无起搏器活性的肠内蠕动同步机制出现功能障碍。Ozaki等人发现，enodotherin B受体缺陷突变小鼠肠尾部肠肌间神经节缺失，观察到肠平滑肌肥大，肠颅向无神经节区域的自发运动减少。Yushi Ito等人研究了胃动素在回肠蠕动中自发传播的机制，发现低浓度胃动素激活阴离子通道介导的钙电流活性增加，以及通过毒蕈碱受体介导的阴离子通道活性显著增加。Takeo Ito研究表明，NO对药物诱导的兔大脑正中动脉收缩有负向控制作用，乙酰胆碱诱导DHF释放增加，激活阿帕胺敏感钾通道，导致动脉平滑肌超极化。Takahama检查了与气管平滑肌张力增加相关的传入神经活动，发现缓激肽影响传入神经活动，速激肽也能改变这种影响。少

项目成果

Fujii, T., Tokutomi, N. et al and Nishi, K.: "Cytoplasmic Ca^<2+> mobilization and Ca^<2+> -dependent membrane currents in dispersed bovine ciliary muscle cells." Current Eye Research. 16. 436-444 (1997)

Fujii, T.、Tokutomi, N. 等人和 Nishi, K.：“分散的牛睫状肌细胞中的细胞质 Ca^2 动员和 Ca^2 依赖性膜电流”。

Yamada, K. et al.: "Electro physiological characterization of a motilin agonist,GM611,on rabbit duodenal smooth muscle." Am. J. Physiol.271. G1003-G1016 (1996)

Yamada, K. 等人：“胃动素激动剂 GM611 对兔十二指肠平滑肌的电生理特性。”

Yamakawa, N. et al and Itoh, T.: "Role of endothelium in regulation of smooth muscle membrane potential and tone in the rabbit middle cerebral artery." Br. J. Pharmacol.121. 1315-1322 (1997)

Yamakawa, N. 等人和 Itoh, T.：“内皮细胞在调节兔大脑中动脉平滑肌膜电位和张力中的作用。”

Kobayashi S: "A smooth muscle nodule producing 10-12 cycle/min regular contractions at the mesenteric border of the pacemaker area in the guinea-pig colon" Arcl.Histol.Cytol. 59. 159-168 (1996)

Kobayashi S：“在豚鼠结肠起搏器区域肠系膜边缘产生 10-12 周期/分钟规则收缩的平滑肌结节”Arcl.Histol.Cytol。

Kobayashi S: "The centenary of the problem of the interstitial cells of Cajal" Acta Anat.Nippon. 71. 629-637 (1996)

Kobayashi S：“卡哈尔间质细胞问题一百周年”Acta Anat.Nippon。