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

蛋白酶激活受体（Protease-activated receptors，PARs）是由凝血酶、胰蛋白酶和类胰蛋白酶等蛋白酶激活的G蛋白偶联的7个跨膜结构域受体，在组织损伤或炎症过程中发挥着多种生理/病理生理作用。我们研究了PARs在消化系统中的生理作用，PAR-1的激活使离体大鼠十二指肠平滑肌产生apamin敏感性舒张，随后收缩。PAR-2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增加的钠渗透性和L型钙通道的激活，部分依赖于酪氨酸激酶、蛋白激酶C和PI 3激酶的激活。然后，PAR-2在体内的激活显着增加外分泌在这两个tissues.In结论，我们的研究表明，PARs存在于小肠，唾液腺和胰腺调节各种生理功能，预测PARs可能是药物开发的目标。

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.