Huang Shih-Che
Department of Internal Medicine, E-Da Hospital, and School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung 824, Taiwan.
Regul Pept. 2012 Nov 10;179(1-3):1-5. doi: 10.1016/j.regpep.2012.08.011. Epub 2012 Sep 4.
Trypsin and thrombin activate proteinase-activated receptors (PARs), which modulate gastrointestinal motility. The common bile duct is exposed to many proteinases that can activate PARs, especially during infection and stone obstruction. We investigated PAR effects on common bile duct motility in vitro. Contraction and relaxation of isolated guinea pig common bile duct strips caused by PAR(1), PAR(2) and PAR(4) agonists were measured using isometric transducers. Reverse transcription polymerase chain reaction (RT-PCR) was performed to determine the expression of PAR(1) and PAR(2). Thrombin and two PAR(1) peptide agonists, TFLLR-NH(2) and SFLLRN-NH(2), evoked moderate relaxation of the carbachol-contracted common bile duct in a concentration-dependent manner. Trypsin and three PAR(2) peptide agonists, 2-furoyl-LIGRLO-NH(2), SLIGKV-NH(2) and SLIGRL-NH(2), generated moderate to marked relaxation as well. The existence of PAR(1) and PAR(2) mRNA in the common bile duct was identified by RT-PCR. Moreover, two PAR(4)-selective agonists, AYPGKF-NH(2) and GYPGQV-NH(2), produced relaxation of the common bile duct. In contrast, all PAR(1), PAR(2) and PAR(4) inactive control peptides did not elicit relaxation. This indicates that PAR(1), PAR(2) and PAR(4) mediate common bile duct relaxation. The thrombin, TFLLR-NH(2), trypsin, and AYPGKF-NH(2)-induced responses were not affected by tetrodotoxin, implying that the PAR effects are not neurally mediated. Our findings provide the first evidence that PAR(1) and PAR(2) mediate whereas agonists of PAR(4) elicit relaxation of the guinea pig common bile duct. Trypsin and thrombin relax the common bile duct. PARs may play an important role in the control of common bile duct motility.
胰蛋白酶和凝血酶可激活蛋白酶激活受体（PARs），而PARs可调节胃肠蠕动。胆总管会接触到许多能够激活PARs的蛋白酶，尤其是在感染和结石梗阻期间。我们在体外研究了PARs对胆总管运动的影响。使用等长换能器测量了PAR(1)、PAR(2)和PAR(4)激动剂引起的离体豚鼠胆总管条的收缩和舒张。进行逆转录聚合酶链反应（RT-PCR）以确定PAR(1)和PAR(2)的表达。凝血酶以及两种PAR(1)肽激动剂TFLLR-NH(2)和SFLLRN-NH(2)，以浓度依赖性方式引起卡巴胆碱收缩的胆总管适度舒张。胰蛋白酶和三种PAR(2)肽激动剂2-呋喃甲酰-LIGRLO-NH(2)、SLIGKV-NH(2)和SLIGRL-NH(2)也产生了中度至显著的舒张。通过RT-PCR鉴定了胆总管中PAR(1)和PAR(2) mRNA的存在。此外，两种PAR(4)选择性激动剂AYPGKF-NH(2)和GYPGQV-NH(2)使胆总管舒张。相比之下，所有PAR(1)、PAR(2)和PAR(4)的无活性对照肽均未引起舒张。这表明PAR(1)、PAR(2)和PAR(4)介导胆总管舒张。凝血酶、TFLLR-NH(2)、胰蛋白酶和AYPGKF-NH(2)诱导的反应不受河豚毒素影响，这意味着PAR的作用不是由神经介导的。我们的研究结果首次证明PAR(1)和PAR(2)介导而PAR(4)激动剂引起豚鼠胆总管舒张。胰蛋白酶和凝血酶使胆总管舒张。PARs可能在胆总管运动的控制中起重要作用。
