NEW DEVELOPMENT OF PHARMACOLOGICAL RESEARCH FOR HISTAMINE : USING MAST CELL DEFICIENT RAT

组胺药理学研究的新进展：利用肥大细胞缺陷大鼠

• 批准号: 07557011
• 负责人: MAEYAMA Kazutaka
• 金额: $ 5.63万
• 依托单位: EHIME UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557011/
• 关键词: MAST CELLS; HISTAMINE; N^<tau>-METHYLHISTAMINE; IN VIVO MICRODIALYSIS; GASTRIC SECRETION; RESTRAINT STRESS; PAW EDEMA; MAST CELL DEFICIENT RATS; N^t-メチルヒスタミン; 炎症; N^7N-メチルヒスタミン; ヒスタミン・ニューロン

In this research project, using mast cell deficient (Ws/Ws) rats, roles of histamine in the pathophysiological conditions such as allergy, gastric ulcer and behavior have been investigated. There are at least two types of histamine pools : one is mast cell-histamine and another is nin-mast cell histamine. As mast cells contain high amount of histamine and are distributed widely, it was difficult to differentiate these two histamine pools. Ws/Ws rats, which has a mutation of c-kit receptor, completely deplete connective tissue type of mast cells. Therefore, histamine contents in tissues of Ws/Ws rats derive from non-mast cell histamine. We can clearly demonstrate the existence of non-mast cell histamine and its roles as follows.1.Histamine content in the brain of Ws/Ws rats is 63% of the congenic (+/+) rats and it decreased to 37% of the control level after treatment of alpha-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase. The remaining content of histamine might … More be due to other pool than mast cells and neuron. (J.Neurochem.65 : 791,1995)2.Using in vivo microdialysis technique, the relationship between edema formation and histamine release in the paw was studied. After treatment of compound 48/80, histamine release sharply occurs in 20 min and decreased gradually through 3 hrs in +/+ rats but no edema formation and histamine release was observed in Ws/Ws rats. Compound 48/80 stimulates histamine release from mast cells and edema formation. (Eur.J.Pharmacol.331 : 237,1997)3.In water immesion stress, plasma histamine levels increased biphasically in normal rats. In the first phase, it reached a peak at 15 min and the second increase was observed between 1.5-6 hrs. After gastrectomy, the second increasein plasma histamine disappeared. In Ws/Ws rats, the water immersion stress causes no first peak and aftr gastrectomy, both increases in plasma histamine disappeared. Non-immunological stimulant causes histamine release from mast cells after water immersion stress. Less

本研究以肥大细胞缺陷型（Ws/Ws）大鼠为研究对象，探讨了组胺在变态反应、胃溃疡和行为学等病理生理学中的作用。组胺池至少有两种类型：一种是肥大细胞-组胺池，另一种是非肥大细胞组胺池。由于肥大细胞含有大量组胺且分布广泛，因此很难区分这两种组胺池。C-kit受体突变的Ws/Ws大鼠，结缔组织型肥大细胞完全耗竭。因此，Ws/Ws大鼠组织中的组胺含量来源于非肥大细胞组胺。结果表明：（1）Ws/Ws大鼠脑组织中组胺含量为同系（+/+）大鼠的63%，经组氨酸脱羧酶抑制剂α-氟甲基组氨酸处理后，其含量降至对照组的37%。组织胺的剩余含量可能 ...更多信息 可能是由于肥大细胞和神经元以外的其他细胞。（J.Neurochem.65：2.采用在体微透析技术，研究了足爪水肿形成与组胺释放的关系。化合物48/80处理后，+/+大鼠中组胺释放在20分钟内急剧发生，并在3小时内逐渐减少，但在Ws/Ws大鼠中未观察到水肿形成和组胺释放。化合物48/80刺激组胺从肥大细胞释放和水肿形成。（Eur.J.Pharmacol.331：237，1997）3.在水浸泡应激中，正常大鼠血浆组胺水平呈双相升高。在第一阶段，它在15分钟时达到峰值，并且在1.5-6小时之间观察到第二次增加。胃切除术后第二次血浆组胺升高消失。Ws/Ws大鼠浸水应激后血浆组胺无第一峰，胃切除后血浆组胺的升高消失。非免疫刺激剂引起水浸应激后肥大细胞释放组胺。少

项目成果

Watanabe, H.: "Transient increase of blood histamine level induced by pentagastrin:Continuous monitoring by in vivo microdialysis" Scand J Gastroenterol. 31. 1144-1150 (1996)

Watanabe, H.：“五肽胃泌素引起的血液组胺水平短暂增加：通过体内微透析进行连续监测”Scand J Gastroenterol。

Guo Y.: "Role of mast cell histamine in formation of rat paw edema." Eur.J.Pharmac.(印刷中). (1997)

郭Y.：“肥大细胞组胺在大鼠爪水肿形成中的作用。”Eur.J.Pharmac.（出版中）。

Goto, Y.: "The release and subsequent synthesis of histamine in a transfected subclone of rat basophilic leukemia cells that expresses human muscarinic m1 receptors" Jpn.J.Pharmacol.69. 167-171 (1995)

Goto, Y.：“表达人毒蕈碱 m1 受体的大鼠嗜碱性白血病细胞转染亚克隆中组胺的释放和随后的合成”Jpn.J.Pharmacol.69。

Guo, Y.: "Role of mast cell histamine in the formation of rat paw edema:a microdialysis study" Eur.J.Pharmacol.331. 237-243 (1997)

郭，Y.：“肥大细胞组胺在大鼠爪水肿形成中的作用：微透析研究”Eur.J.Pharmacol.331。

Goto Y.: "Insulin-like action of chromate on glucose transport in isolated rat adipocytes." Jpn.J.Pharmacol.67. 365-368 (1995)

Goto Y.：“铬酸盐对离体大鼠脂肪细胞中葡萄糖转运的胰岛素样作用。”