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.

蛋白酶激活的受体（PARS），G蛋白偶联的七个跨膜结构域受体被某些蛋白酶（例如凝血酶，胰蛋白酶和胰蛋白酶胰蛋白酶）激活，扮演着各种生理/病理生理学作用，尤其是在组织损伤或炎症过程中。我们研究了PAR在养殖系统中的生理作用。PAR-1产生的Apamin敏感性松弛的激活，然后在分离的大鼠十二指肠平滑肌中收缩。 PAR-2激活仅引起收缩。 PAR-4没有产生响应。 PAR-1介导的收缩在很大程度上取决于钠渗透性的增加和L型钙通道的激活，部分是酪氨酸激酶，蛋白激酶C和PI3激酶的激活。接下来，我们在唾液腺和pancreas中检测到PAR-2的mRNA。然后，在两个组织中的体内激活显着增强了外分泌分泌。总之，我们的研究表明，在小肠，唾液腺和胰腺中存在的PARS会调节各种生理功能，预测PAR可以成为药物开发的靶标。

项目成果

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.: "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.: "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)

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.