Evaluation of metaiodobenzylguanidine uptake by the norepinephrine, dopamine and serotonin transporters.
Metaiodobenzylguanidine (MIBG) is taken up by sympathetic neurons, but the precise mechanism of uptake has not been elucidated. Uptake of monoamines by presynaptic neurons is mediated by plasma membrane proteins, the monoamine transporters. The human norepinephrine transporter (hNET), the bovine dopamine transporter (bDAT) and the rat serotonin transporter (r5HTT) have been cloned, sequenced and expressed in various cell lines. This study involves the measurement of MIBG uptake by cell lines that have been transfected with complementary DNAs encoding these monoamine transporters. At 20 nM MIBG, hNET transfected cells demonstrate a ninefold greater uptake of MIBG than nontransfected cells. MIBG uptake in hNET transfected cells is inhibited by 3 x 10(-6) M norepinephrine (87% inhibition) and by hNET transport inhibitors: 10(-7) M desipramine (94% inhibition) and 10(-7) M mazindol (97% inhibition). hNET transfected cells exhibit a Km for MIBG transport of 264 nM. Percent nonspecific uptake rises with increasing concentrations of MIBG while specific uptake is saturable. There is no significant uptake by bDAT or r5HTT. The NET appears to be responsible for the specific uptake of MIBG.
Glowniak
J V
JV
Nuclear Medicine Service, Veterans' Affairs Medical Center, Portland, OR 97207.
Kilty
J E
JE
Amara
S G
SG
Hoffman
B J
BJ
Turner
F E
FE
D019797:3-Iodobenzylguanidine; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D050483:Dopamine Plasma Membrane Transport Proteins; D000882:Haplorhini; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007462:Iodobenzenes / Q000493:pharmacokinetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins; D051381:Rats; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters; D014162:Transfection
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C493226:Slc6a2 protein, rat; C493232:Slc6a4 protein, rat; D027981:Symporters; D019797:3-Iodobenzylguanidine; D009638:Norepinephrine