Jakubík J, Bacáková L, el-Fakahany E E, Tucek S
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague.
FEBS Lett. 1995 Dec 18;377(2):275-9. doi: 10.1016/0014-5793(95)01360-1.
We investigated whether muscarinic receptors of the M1-M4 receptor subtypes are constitutively active. We have found that the synthesis of cyclic AMP was enhanced by the muscarinic antagonists atropine and N-methylscopolamine (NMS) in Chinese hamster ovary (CHO) cells stably transfected with human m2 and m4 muscarinic receptor genes and in rat cardiomyocytes expressing the M2 receptor subtype, and that the production of inositol phosphates was inhibited by atropine and NMS in CHO cells stably transfected with human m1 and m3 and with rat m1 muscarinic receptor genes. The muscarinic antagonists quinuclidinyl benzilate and AF-DX 116 had no effect in some cases and acted like atropine and NMS in others. We conclude that the M1-M4 subtypes of muscarinic receptors are constitutively active in the CHO cell lines expressing them and in cardiomyocytes and that atropine and NMS act as negative antagonists on these receptor subtypes by stabilizing them in the inactive conformation.
我们研究了M1 - M4受体亚型的毒蕈碱受体是否组成性激活。我们发现，在中国仓鼠卵巢（CHO）细胞中稳定转染人m2和m4毒蕈碱受体基因，以及在表达M2受体亚型的大鼠心肌细胞中，毒蕈碱拮抗剂阿托品和N - 甲基东莨菪碱（NMS）可增强环磷酸腺苷（cAMP）的合成；而在稳定转染人m1和m3以及大鼠m1毒蕈碱受体基因的CHO细胞中，阿托品和NMS可抑制肌醇磷酸的产生。毒蕈碱拮抗剂樟柳碱和AF - DX 116在某些情况下无作用，而在其他情况下作用类似阿托品和NMS。我们得出结论，毒蕈碱受体的M1 - M4亚型在表达它们的CHO细胞系和心肌细胞中是组成性激活的，并且阿托品和NMS通过将这些受体亚型稳定在非活性构象上，作为负性拮抗剂发挥作用。
