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神经内分泌性胃肠肿瘤细胞中多巴胺受体和转运体的表达

Expression of dopamine receptors and transporter in neuroendocrine gastrointestinal tumor cells.

作者信息

Lemmer K, Ahnert-Hilger G, Höpfner M, Hoegerle S, Faiss S, Grabowski P, Jockers-Scherübl M, Riecken E O, Zeitz M, Scherübl H

机构信息

Med. Klinik I, Universitätsklinikum Benjamin Franklin, FU, Berlin, Germany.

出版信息

Life Sci. 2002 Jun 28;71(6):667-78. doi: 10.1016/s0024-3205(02)01703-4.

DOI:10.1016/s0024-3205(02)01703-4
PMID:12072155
Abstract

C-11- or F-18-DOPA positron emission tomography (DOPA PET) is a new sensitive imaging technique for small neuroendocrine gastrointestinal tumors which evaluates the decarboxylase activity. To further characterize the dopaminergic system in neuroendocrine gastrointestinal tumor cells, we investigated the expression of both dopamine receptors and the transmembrane dopamine transporter (DAT) in the human neuroendocrine pancreatic cell line BON and in the neuroendocrine gut cell line STC-1. Both BON and STC-1 cells expressed mRNA of the dopamine receptors D2-D5 and DAT. mRNA of the dopamine receptor D1 was detected in BON cells only. Both in BON and STC-1 cells, expression of D2 and D5 receptors and DAT was also demonstrated immunocytochemically. For functional receptor characterization intracellular cAMP levels ([cAMP]i) were determined. Whereas in STC-1 cells dopamine and the D1-like (D1/D5) receptor agonist SKF 38393 increased [cAMP]i, [cAMP]i was decreased by dopamine or the D2-like (D2-D4) receptor agonist quinpirole in BON cells. Functional DAT activity was, however, not detected in either cell line. The presence of both dopamine receptors and of the DAT suggests an autocrine and/or paracrine function of dopamine in neuroendocrine gastrointestinal tumor cells. Yet neither the transmembrane dopamine transporter nor dopamine receptors are likely to contribute to positive DOPA PET imaging of neuroendocrine gastrointestinal tumors. However, these molecules may be of diagnostic importance when applying other dopaminergic system tracers.

摘要

碳-11或氟-18-多巴正电子发射断层扫描(DOPA PET)是一种用于评估脱羧酶活性的新型敏感成像技术,可用于检测小的神经内分泌性胃肠道肿瘤。为了进一步表征神经内分泌性胃肠道肿瘤细胞中的多巴胺能系统,我们研究了多巴胺受体和跨膜多巴胺转运体(DAT)在人神经内分泌胰腺细胞系BON和神经内分泌肠道细胞系STC-1中的表达。BON细胞和STC-1细胞均表达多巴胺受体D2 - D5和DAT的mRNA。仅在BON细胞中检测到多巴胺受体D1的mRNA。在BON细胞和STC-1细胞中,D2和D5受体以及DAT的表达也通过免疫细胞化学得到证实。为了对功能性受体进行表征,测定了细胞内cAMP水平([cAMP]i)。在STC-1细胞中,多巴胺和D1样(D1 / D5)受体激动剂SKF 38393可增加[cAMP]i,而在BON细胞中,多巴胺或D2样(D2 - D4)受体激动剂喹吡罗可降低[cAMP]i。然而,在这两种细胞系中均未检测到功能性DAT活性。多巴胺受体和DAT的存在表明多巴胺在神经内分泌性胃肠道肿瘤细胞中具有自分泌和/或旁分泌功能。然而,跨膜多巴胺转运体和多巴胺受体都不太可能对神经内分泌性胃肠道肿瘤的DOPA PET阳性成像有贡献。然而,当应用其他多巴胺能系统示踪剂时,这些分子可能具有诊断重要性。

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