Identification and pharmacological characterization of a specific agmatine transport system in human tumor cell lines
Identification and pharmacological characterization of a specific agmatine transport system in human tumor cell lines
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DOI：
10.1196/annals.1304.008
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发表时间：
2003-01-01
期刊：
影响因子：
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通讯作者：
Göthert, M
中科院分区：
文献类型：
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作者：
Molderings, GJ;Brüss, M;Göthert, M
酚妥拉明、咪唑克生、可乐定、1，3-二(2-甲苯基)胍、组胺、腐胺、精胺和亚精胺可抑制[C-14]胍胺在6种人肠道肿瘤细胞系和SK-MG-1胶质瘤细胞系中的特异性积聚。皮质酮、地塞帕明、O-甲基异丙肾上腺素、环唑啉、莫索尼定、L-精氨酸、L-赖氨酸、维拉帕米、硝苯地平、氯化镉、恩丹西酮和L-卡尼汀均不能抑制特异性的[C-14]胍丁胺蓄积，因此排除了它是由氨基酸或单胺载体、腐胺载体、5-HT3受体通道、钙离子通道或有机阳离子转运体OCT1、OCT2、OCT3、OCTN1或OCTN2介导的。这一结论得到了以下发现的支持：与未转染的细胞相比，转导hOCT1、hOCT2或hOCT3基因的HEK293细胞并没有增加特异性的[14C]胍丁胺蓄积。这些数据表明，胍丁胺是由特定的胍丁胺转运体积累的。由于与外源性胍丁胺孵育24小时后，所有细胞系细胞内的胍丁胺含量都增加了基础内源性含量的倍数，因此胍丁胺摄取系统可能与调节人体细胞内和细胞外的胍丁胺浓度有关。
Specific accumulation of [C-14]agmatine in six human intestinal tumor cell lines and in the glioma cell line SK-MG-1 was inhibited by phentolamine, idazoxan, clonidine, 1,3-di-(2-tolyl)guanidine, histamine, putrescine, spermine and spermidine. Corticosterone, desipramine, O-methylisoprenaline, cirazoline, moxonidine, L-arginine, L-lysine, verapamil, nifedipine, CdCl2, ondansetron, and L-carnitine failed to inhibit specific [C-14]agmatine accumulation, thus excluding that it is mediated by amino acid or monoamine carriers, by the putrescine carrier, by 5-HT3 receptor channels, by Ca2+ channels or by the organic cation transporters OCT1, OCT2, OCT3, OCTN1, or OCTN2. This conclusion is supported by the finding that transfection of HEK293 cells with cDNA encoding either hOCT1, hOCT2, or hOCT3 did not enhance specific [14C]agmatine accumulation compared to nontransfected cells. The data suggest that agmatine is accumulated by a specific agmatine transporter. Since incubation with exogenous agmatine for 24 hours increased intracellular agmatine content in all cell lines by a multiple of the basal endogenous content, the agmatine uptake system may be relevant for the regulation of the intra- and extracellular concentration of agmatine in humans.