Ackerman M S, Roeske W R, Heck R J, Korc M
Department of Internal Medicine, University of Arizona College of Medicine, Tucson.
Pancreas. 1989;4(3):363-70. doi: 10.1097/00006676-198906000-00014.
Five human pancreatic carcinoma cell lines were screened for the presence of muscarinic cholinergic receptors (mAChRs), using [3H]N-methylscopolamine ([3H]NMS). T3M4 and COLO-357 cells exhibited specific, high-affinity binding to mAChRs. A small amount of [3H]NMS also bound in PANCI and ASPC-I cells, but not in MIA PaCa-2 cells. Atropine, pirenzepine (PZ), and 11-[[2-[(diethylamino) methyly]-1-piperidinyl] acetyl]-5, 11-dihydro-6H-pyrido-[2, 3-b] [1, 4] benzodiazepine-6-one (AF-DX 116) inhibited [3H]NMS binding and carbachol-mediated [3H]inositol monophosphate formation in both T3M4 and COLO-357 cells. The order of inhibition was: atropine greater than PZ greater than AF-DX 116. Carbachol did not alter [3H]inositol monophosphate formation in the other cell lines. These findings suggest that the mAChRs expressed in some human pancreatic cancer cells exhibit the pharmacologic characteristics of a muscarinic receptor subtype with an intermediate affinity for PZ and a lower affinity for AF-DX 116 and are functionally coupled to activation of phospholipid hydrolysis.
使用[3H]N-甲基东莨菪碱（[3H]NMS）对5种人胰腺癌细胞系进行毒蕈碱型胆碱能受体（mAChRs）检测。T3M4和COLO-357细胞表现出对mAChRs的特异性、高亲和力结合。少量的[3H]NMS也能结合于PANCI和ASPC-I细胞，但不能结合于MIA PaCa-2细胞。阿托品、哌仑西平（PZ）和11-[[2-[(二乙氨基)甲基]-1-哌啶基]乙酰基]-5,11-二氢-6H-吡啶并-[2,3-b][1,4]苯二氮䓬-6-酮（AF-DX 116）可抑制T3M4和COLO-357细胞中[3H]NMS的结合以及卡巴胆碱介导的[3H]肌醇单磷酸的形成。抑制顺序为：阿托品＞PZ＞AF-DX 116。卡巴胆碱未改变其他细胞系中[3H]肌醇单磷酸的形成。这些发现表明，在一些人胰腺癌细胞中表达的mAChRs表现出对PZ具有中等亲和力、对AF-DX 116具有较低亲和力的毒蕈碱受体亚型的药理学特性，并且在功能上与磷脂水解的激活相关联。
