Broquet P, Baubichon-Cortay H, George P, Peschard M J, Louisot P
INSERM U. 189, Laboratoire de Biochimie Générale et Médicale, Faculté de Médecine Lyon-Sud, Oullins, France.
J Neurochem. 1990 Feb;54(2):388-94. doi: 10.1111/j.1471-4159.1990.tb01885.x.
The tricyclic antidepressant desipramine, when added to culture medium, gave rise in C6 rat glioma cells to a decrease of the activity of the enzyme asialofetuin sialyltransferase. The inhibition was dose and time dependent and was observed in both multiplying cells and cells blocked with 2 mM thymidine or depletion of amino acids. This inhibition was rather specific to the sialyltransferase, as under the conditions where this enzyme was inhibited up to 70%, other enzymes such as dolichol phosphate mannose synthetase, glutamine synthetase, and glycerol phosphate dehydrogenase remained unaffected. This inhibition was not reversed after removal of desipramine from the medium and was not observed by direct addition of desipramine to the sialyltransferase incubation assay. Under the same conditions, W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide], which is known to be a potent calmodulin antagonist and an inhibitor of calmodulin-dependent kinases, gave the same concentration-dependent inhibition profile of sialyltransferase as desipramine, whereas H-7 [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine], which is an inhibitor of protein kinase C and cyclic nucleotide-dependent kinases, had no effect. So, it is suggested that desipramine inhibits the sialyltransferase activity in C6 glioma cells through a calmodulin-dependent system.
三环类抗抑郁药地昔帕明添加到培养基中时，会使C6大鼠胶质瘤细胞中的去唾液酸胎球蛋白唾液酸转移酶活性降低。这种抑制作用呈剂量和时间依赖性，在增殖细胞以及用2 mM胸苷阻断或氨基酸耗尽的细胞中均能观察到。这种抑制作用对唾液酸转移酶具有相当的特异性，因为在该酶被抑制高达70%的条件下，其他酶如多萜醇磷酸甘露糖合成酶、谷氨酰胺合成酶和甘油磷酸脱氢酶不受影响。从培养基中去除地昔帕明后，这种抑制作用不会逆转，并且在唾液酸转移酶孵育试验中直接添加地昔帕明时也未观察到这种抑制作用。在相同条件下，已知作为有效的钙调蛋白拮抗剂和钙调蛋白依赖性激酶抑制剂的W-7 [N-(6-氨基己基)-5-氯-1-萘磺酰胺]，对唾液酸转移酶产生了与地昔帕明相同的浓度依赖性抑制曲线，而作为蛋白激酶C和环核苷酸依赖性激酶抑制剂的H-7 [1-(5-异喹啉基磺酰基)-2-甲基哌嗪]则没有作用。因此，有人提出地昔帕明通过钙调蛋白依赖性系统抑制C6胶质瘤细胞中的唾液酸转移酶活性。
