Español Alejandro J, Sales María E
Departamento de Inmunobiología, Area Investigación, Instituto de Oncología Angel H. Roffo, Universidad de Buenos Aires, CP 1417, Buenos Aires, Argentina.
Int J Mol Med. 2004 Feb;13(2):311-7.
We described that two different murine mammary adenocarcinoma cell lines, LM3 and LM2 constitutively expressed muscarinic acetylcholine receptors (mAchR). We here demonstrate, by competitive binding experiments with the tritiated muscarinic antagonist quinuclidinyl benzilate that M2 subtype predominates in both tumor cell lines. Concordantly immunoblotting assays indicate that mAchR exhibit the following order of expression: M2 > M4 > M3 > M1 >> M5 in both tumor cell lines. Activation of mAchR with carbachol (CARB) increased proliferation in both tumor cell lines in a concentration dependent manner. In LM3 cells CARB promoted proliferation via M3 receptor activation via inositol 1,4,5-triphosphate and nitric oxide production. CARB-induced LM2 cells proliferation needed both M2 and M1 receptor activation, promoting prostaglandin E2 liberation and arginase catabolism respectively, both of them involved in tumor cell growth.
我们曾描述过，两种不同的小鼠乳腺腺癌细胞系LM3和LM2组成性表达毒蕈碱型乙酰胆碱受体（mAchR）。我们在此通过用氚标记的毒蕈碱拮抗剂喹核醇基苯甲酸酯进行竞争性结合实验证明，M2亚型在这两种肿瘤细胞系中占主导地位。一致地，免疫印迹分析表明，在这两种肿瘤细胞系中，mAchR的表达呈现以下顺序：M2＞M4＞M3＞M1＞＞M5。用卡巴胆碱（CARB）激活mAchR以浓度依赖性方式增加了这两种肿瘤细胞系的增殖。在LM3细胞中，CARB通过肌醇1,4,5 -三磷酸和一氧化氮的产生经由M3受体激活促进增殖。CARB诱导的LM2细胞增殖需要M2和M1受体的激活，分别促进前列腺素E2的释放和精氨酸酶的分解代谢，二者均参与肿瘤细胞生长。
