Naoi M, Takahashi T, Ichinose H, Wakabayashi K, Sugimura T, Nagatsu T
Department of Biochemistry, Nagoya University School of Medicine, Japan.
Neurosci Lett. 1989 May 8;99(3):317-22. doi: 10.1016/0304-3940(89)90466-7.
Heterocyclic amines, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), are known to be produced in food by cooking and are carcinogenic. These amines were found to be accumulated in clonal rat pheochromocytoma PC12h cells and to reduce enzyme activity related to catecholamine synthesis. The mechanism of uptake of these heterocyclic amines into PC12h cells was studied. The uptake was dependent on the incubation time, the amount of the cells, and the concentrations of Trp-P-1 and Trp-P-2 in the incubation mixture. The uptake of these amines was saturable with their concentrations, and the uptake velocity followed the Michaelis-Menten equation, indicating that the uptake was mediated by a transporting protein. The uptake was inhibited by dopamine and serotonin, but not by noradrenaline. Involvement of the dopamine uptake system in uptake of the heterocyclic amines was further indicated by the fact that nomifensine and mazindol, specific inhibitors of dopamine uptake, reduced the uptake, but sulpiride, an antagonist of D2 receptor, did not. The significance of the uptake of the carcinogenic heterocyclic amines was discussed in relation to their possible neurotoxicity in the human brain.
杂环胺，3-氨基-1,4-二甲基-5H-吡啶并[4,3-b]吲哚（Trp-P-1）和3-氨基-1-甲基-5H-吡啶并[4,3-b]吲哚（Trp-P-2），已知在烹饪食物过程中产生且具有致癌性。这些胺类物质被发现可在大鼠克隆嗜铬细胞瘤PC12h细胞中蓄积，并降低与儿茶酚胺合成相关的酶活性。对这些杂环胺进入PC12h细胞的摄取机制进行了研究。摄取取决于孵育时间、细胞数量以及孵育混合物中Trp-P-1和Trp-P-2的浓度。这些胺类物质的摄取与其浓度呈饱和关系，摄取速度符合米氏方程，表明摄取是由转运蛋白介导的。摄取受到多巴胺和5-羟色胺的抑制，但不受去甲肾上腺素的抑制。多巴胺摄取系统参与杂环胺摄取这一点进一步由以下事实表明：多巴胺摄取的特异性抑制剂诺米芬辛和吗茚酮降低了摄取，但D2受体拮抗剂舒必利则没有。针对致癌性杂环胺的摄取，结合其在人脑中可能存在的神经毒性进行了讨论。
