Smith A J, Patel S, Freedman S B
Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Eur J Pharmacol. 1994 Apr 15;267(2):215-23. doi: 10.1016/0922-4106(94)90173-2.
Cholecystokinin receptors on GH3 rat anterior pituitary cells have been characterised using radioligand binding and Ca2+ mobilisation. [125I]Bolton Hunter CCK-8s (BHCCK) bound dose dependently to GH3 cells (Kd 85 pM, Bmax 23 fmol/mg protein). Competition curves with CCK-8s (IC50 2.4 nM), pentagastrin (IC50 25 nM) and devazepide (IC50 820 nM), were consistent with a population predominantly of CCKB receptors. Binding of [125I]BHCCK to lysed cells was inhibited by 10 microM GTP-gamma-S and 10 microM GppNHp, suggesting the receptor was linked to a guanine nucleotide binding protein. Intracellular Ca2+ mobilisation was a functional consequence of CCKB receptor activation in GH3 cells using the fluorescent dye fura-2. CCK-8s (0.1 nM-1 microM) and the selective CCKB receptor agonist, pentagastrin, (0.1 nM-100 microM) dose dependently increased intracellular Ca2+ with a similar maximal increase of 2.85-fold and 2.77-fold respectively. Response to a submaximal dose of the CCKB receptor agonist pentagastrin (100 nM) was dose dependently blocked by the CCKB receptor antagonist L-365,260. GH3 cells may therefore provide a useful model to study CCKB receptor coupling in a pituitary cell line.
已利用放射性配体结合和钙离子动员对GH3大鼠垂体前叶细胞上的胆囊收缩素受体进行了表征。[125I]博尔顿·亨特CCK-8s(BHCCK)与GH3细胞的结合呈剂量依赖性(解离常数85 pM,最大结合量23 fmol/mg蛋白)。CCK-8s(半数抑制浓度2.4 nM)、五肽胃泌素(半数抑制浓度25 nM)和地伐西匹(半数抑制浓度820 nM)的竞争曲线与主要为CCKB受体的群体一致。10 microM的GTP-γ-S和10 microM的GppNHp可抑制[125I]BHCCK与裂解细胞的结合,提示该受体与鸟嘌呤核苷酸结合蛋白相偶联。使用荧光染料fura-2,细胞内钙离子动员是GH3细胞中CCKB受体激活的功能结果。CCK-8s(0.1 nM - 1 microM)和选择性CCKB受体激动剂五肽胃泌素(0.1 nM - 100 microM)剂量依赖性地增加细胞内钙离子,最大增加倍数分别为2.85倍和2.77倍。对CCKB受体激动剂五肽胃泌素(100 nM)的亚最大剂量反应被CCKB受体拮抗剂L-365,260剂量依赖性地阻断。因此,GH3细胞可能为研究垂体细胞系中的CCKB受体偶联提供一个有用的模型。