ROLES OF PROTEASE-ACTIVATED RECEPTORS IN THE ALIMENTARY SYSTEMS : PARTICIPATION IN THE MODULATION OF FUNCTIONS IN THE SALIVARY GLANDS, PANCREAS AND SMALL INTESTINE

消化系统中蛋白酶激活受体的作用：参与唾液腺、胰腺和小肠的功能调节

• 批准号: 11672283
• 负责人: KAWABATA Atsufumi
• 金额: $ 1.34万
• 依托单位: KINKI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672283/
• 关键词: protease-activated receptor; protease; PAR; gastrointestinal motility; salivation; pancreatic secretion; 消化器; 唾液; 膵液; アミラーゼ; 小腸運動; アパミン; カルシウムチャネル; カリウムチャネル; トロンビン; トリプシン

Protease-activated receptors (PARs), G protein-coupled seven trans-membrane domain receptors activated by certain proteases such as thrombin, trypsin and tryptase, play various physiological/pathophysiological roles especially during tissue injury or inflammation. We investigated the physiological roles of PARs in the alimentary systems.Activation of PAR-1 produced apamin-sensitive relaxation followed by contraction in the isolated rat duodenal smooth muscle. PAR-2 activation elicited only contraction. PAR-4 produced no response. The PAR-1-mediated contraction was largely dependent on increased sodium permeability and activation of L-type calcium channels, and in part on activation of tyrosine kinase, protein kinase C and PI3 kinase.We next detected mRNA for PAR-2 in the salivary glands and pancreas. Then, activation of PAR-2 in vivo markedly augmented exocrine secretion in both the tissues.In conclusion, our study demonstrates that PARs present in the small intestine, salivary glands and pancreas modulate various physiological functions, predicting that PARs could be targets for drug development.

蛋白水解酶激活受体(PARs)是G蛋白偶联的七种跨膜区受体，由凝血酶、胰酶和胰蛋白酶等酶激活，在组织损伤或炎症过程中发挥着不同的生理/病理生理作用。我们研究了PAR-1在消化系统中的生理作用。在分离的大鼠十二指肠平滑肌上，PAR-1激活后产生阿帕明敏感的松弛和收缩。PAR-2的激活只引起收缩。PAR-4没有反应。PAR-1介导的收缩在很大程度上依赖于钠离子通透性的增加和L型钙通道的激活，部分依赖于酪氨酸激酶、蛋白激酶C和PI3激酶的激活。在体内，PAR-2的激活显著增加了这两个组织的外分泌。综上所述，我们的研究表明，存在于小肠、唾液腺和胰腺中的PARs调节着各种生理功能，预测PARs可能成为药物开发的靶点。

项目成果

Kawabata,A. et al.: "Activation of protease-activated receptor-2 (PAR-2) triggers mucin secretion in the rat sublingual gland"Biochemical and Biophysical Research Communications. 270. 298-302 (2000)

川端康成，A.

Kawabata,A. et al.: "Determination of mucin in salivary glands using sialic acid as the marker by high performance Liquid chromatography with fluorometric detection"Anal.Biochem.. 283. 119-121 (2000)

川端康成，A.

Kawabata,A. et al.: "Protease-activated receptor-2-(PAR-2) : regulation of salivary and pancreatic exocrine secretion in vivo in rats and mice"Br.J.Pharmacol.. 129. 1627-1632 (2000)

川端康成，A.

Kawabata,A., et al.: "Modulation by protease-activated receptors of the rat duodenal motility in vitro : possible mechanisms underlying the evoked contraction and relaxation"British Journal of Pharmacology. 128. 865-872 (1999)

Kawabata,A.等人：“体外大鼠十二指肠运动的蛋白酶激活受体的调节：诱发收缩和松弛的可能机制”英国药理学杂志。

Kawabata, A.et al.: "Characterization of the protease-activated receptor-1-mediated contraction and relaxation in the rat duodenal smooth muscle"Life Sci.. 67. 2521-2530 (2000)

Kawabata, A. 等人：“大鼠十二指肠平滑肌中蛋白酶激活受体 1 介导的收缩和松弛的表征”Life Sci.. 67. 2521-2530 (2000)