Expression of dopamine receptors and transporter in neuroendocrine gastrointestinal tumor cells.
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.
Lemmer
K
K
Med. Klinik I, Universitätsklinikum Benjamin Franklin, FU, Berlin, Germany.
Ahnert-Hilger
G
G
Höpfner
M
M
Hoegerle
S
S
Faiss
S
S
Grabowski
P
P
Jockers-Scherübl
M
M
Riecken
E O
EO
Zeitz
M
M
Scherübl
H
H
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D005770:Gastrointestinal Neoplasms; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000235:genetics*; D051379:Mice; D009419:Nerve Tissue Proteins; D018358:Neuroendocrine Tumors / Q000235:genetics*; D010190:Pancreatic Neoplasms; D019257:Quinpirole / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D011954:Receptors, Dopamine / Q000235:genetics*; D017447:Receptors, Dopamine D1 / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; C493215:Slc6a3 protein, mouse; D005576:Colforsin; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000242:Cyclic AMP; D004298:Dopamine