CCK receptor dysfunction in muscle membranes from human gallbladders with cholesterol stones.
CCK receptor dysfunction in muscle membranes from human gallbladders with cholesterol stones.
复制标题
患有胆固醇结石的人胆囊肌膜中 CCK 受体功能障碍。
DOI：
10.1152/ajpgi.1999.276.6.g1401
复制
发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Behar,J
中科院分区：
文献类型：
--
作者：
Xiao,ZL;Chen,Q;Amaral,J;Biancani,P;Jensen,RT;Behar,J
与胆色素结石患者相比，胆固醇结石患者表现出由作用于跨膜受体的激动剂引起的肌肉收缩受损、膜胆固醇含量增加以及胆固醇与磷脂比异常。本研究采用放射受体分析和交联法研究胆囊肌膜CCK受体的功能。Scatchard分析显示胆固醇组的最大特异结合（Bmax）显著低于胆色素结石组（0.18 ± 0.07vs.0.38 ± 0.05pmol/mg蛋白，P <0.05）。相比之下，胆固醇胆囊中CCK的亲和力高于胆色素结石胆囊（0.18 ± 0.06 vs. 1.2 ± 0.23 nM）。在CCK-A受体拮抗剂[3H] L-364，718的结合研究中观察到类似结果。交联和饱和结合的研究也表明，胆囊胆囊胆固醇结石的CCK结合显着减少。与无胆固醇脂质体孵育后，这些异常是可逆的。与无胆固醇脂质体孵育后，Bmax增加（P <0.01），解离常数降低（P <0.001）。总之，与胆固醇结石相比，胆固醇结石患者胆囊CCK受体结合受损。这些变化通过去除多余的膜胆固醇而逆转。这些受体的改变可能导致胆固醇结石患者胆囊肌收缩力的缺陷。
Human gallbladders with cholesterol stones exhibit impaired muscle contraction induced by agonists that act on transmembrane receptors, increased membrane cholesterol content, and abnormal cholesterol-to-phospholipid ratio compared with those with pigment stones. The present study was designed to investigate the functions of the CCK receptor of gallbladder muscle membranes by radioreceptor assay and cross-linking.125I-labeled CCK-8 binding was time-dependent, competitive, and specific. Scatchard analysis showed that the maximum specific binding (Bmax) was significantly decreased in cholesterol compared with pigment stone gallbladders (0.18 ± 0.07 vs. 0.38 ± 0.05 pmol/mg protein,P< 0.05). In contrast, the affinity for CCK was higher in cholesterol than pigment stone gallbladders (0.18 ± 0.06 vs. 1.2 ± 0.23 nM). Similar results were observed in binding studies with the CCK-A receptor antagonist [3H]L-364,718. Cross-linking and saturation binding studies also showed significantly less CCK binding in gallbladders with cholesterol stones. These abnormalities were reversible after incubation with cholesterol-free liposomes. The Bmaxincreased (P< 0.01) and the dissociation constant decreased (P< 0.001) after incubation with cholesterol-free liposomes. In conclusion, human gallbladders with cholesterol stones have impaired CCK receptor binding compared with those with pigment stones. These changes are reversed by removal of the excess membrane cholesterol. These receptor alterations may contribute to the defective contractility of the gallbladder muscle in patients with cholesterol stones.