Schjoldager B T
Rigshospitalet, University Hospital of Copenhagen, Denmark.
Ann N Y Acad Sci. 1994 Mar 23;713:207-18. doi: 10.1111/j.1749-6632.1994.tb44067.x.
Cholecystokinin may play a role in regulation of interdigestive motility, but this still remains to be investigated. CCK constitutes the major hormonal stimulus for postprandial gallbladder emptying. CCK exerts its contractile effects mainly through interaction directly with receptors on the gallbladder smooth muscle cells in the muscle layer, but also through interaction with cholinergic nerves extrinsic and/or intrinsic in nature. Furthermore, CCK can enhance ongoing nicotinic ganglionic transmission occurring in the serosal layer by release of acetylcholine. CCK interaction with the gallbladder smooth muscle CCKA receptor was studied in further detail. CCK contracts strips of gallbladder muscle in a concentration-dependent way with a potency in the nanomolar range in all tested species. The potency is 1,000-fold better than that of gastrin; thus, the receptor is of type CCKA. CCK binding to this receptor is specific and of high affinity, 1,000-fold better than that of gastrin with no differences between the tested species including bovine, porcine, and human. Also, CCK binding affinity was independent of age, gender, or weight of the person and pathology of the human gallbladder. The biochemistry of the CCKA receptor varies between the tested species (bovine and human). Both CCKA receptors are heavily glycosylated, but of different size and carbohydrate content. The bovine CCKA receptor is of apparent size M(r) = 70-85 kD with N-linked complex carbohydrates and sialic acids. The human CCKA receptor is of M(r) = 85-95 kD, with N-linked complex carbohydrates, but no sialic acids. They both have a protein core of apparent size M(r) = 43 kD, with almost identically sized fragments after enzymatic cleavage. Probably the protein cores contain the receptor binding region, which seems well preserved between species. CCK and the CCKA gallbladder muscularis receptor are main regulators of postprandial gallbladder emptying. The biochemistry of the CCKA gallbladder smooth muscle receptor is in accord with newly generated data of purification and cloning of the rat pancreatic CCKA receptor.
胆囊收缩素可能在消化间期运动的调节中发挥作用，但这仍有待研究。胆囊收缩素是餐后胆囊排空的主要激素刺激因素。胆囊收缩素主要通过直接与肌层胆囊平滑肌细胞上的受体相互作用来发挥其收缩作用，但也通过与外在和/或内在的胆碱能神经相互作用来实现。此外，胆囊收缩素可通过释放乙酰胆碱增强浆膜层中正在进行的烟碱样神经节传递。对胆囊收缩素与胆囊平滑肌CCKA受体的相互作用进行了更详细的研究。胆囊收缩素以浓度依赖性方式收缩胆囊肌条，在所有测试物种中其效力处于纳摩尔范围。其效力比胃泌素高1000倍；因此，该受体为CCKA型。胆囊收缩素与该受体的结合具有特异性且亲和力高，比胃泌素高1000倍，在所测试的物种（包括牛、猪和人）之间没有差异。此外，胆囊收缩素的结合亲和力与年龄、性别、人的体重以及人类胆囊的病理状况无关。CCKA受体的生物化学在测试物种（牛和人）之间有所不同。两种CCKA受体都高度糖基化，但大小和碳水化合物含量不同。牛的CCKA受体表观大小为M(r)=70 - 85 kD，具有N - 连接的复合碳水化合物和唾液酸。人的CCKA受体为M(r)=85 - 95 kD，具有N - 连接的复合碳水化合物，但没有唾液酸。它们都有一个表观大小为M(r)=43 kD的蛋白质核心，酶切后片段大小几乎相同。可能蛋白质核心包含受体结合区域，该区域在物种之间似乎保存得很好。胆囊收缩素和CCKA胆囊肌层受体是餐后胆囊排空的主要调节因子。CCKA胆囊平滑肌受体的生物化学与大鼠胰腺CCKA受体纯化和克隆的最新数据一致。
