Hydroxytyrosol increases norepinephrine transporter function in pheochromocytoma cells.
BACKGROUND
The norepinephrine transporter is responsible for the intracellular uptake of (131)I- iodometaiodobenzylguanidine ((131)I-MIBG), which is used for the diagnostic localization and treatment of pheochromocytomas as well as other tumors such as neuroblastomas and carcinoids. This agent is variably delivered into tumor cells by the norepinephrine transporter, but few studies have shown treatments that work to increase norepinephrine transporter activity. The objective of the present study was to test the possible beneficial effects of hydroxytyrosol in enhancing norepinephrine transporter function, which may have implications for its combined use with (131)I-MIBG in the diagnosis and treatment of pheochromocytomas.


METHODS
Rat pheochromocytoma PC12 cells were labeled with [(3)H]-norepinephrine in the presence or absence of different concentrations of hydroxytyrosol, a naturally occurring compound with strong antioxidant properties, followed by measurements of uptake and release of radiolabeled norepinephrine.


RESULTS
Hydroxytyrosol pronouncedly increased norepinephrine transporter activity, with the rapid onset excluding effects on norepinephrine transporter expression levels. Concomitant with increased norepinephrine transporter activity, hydroxytyrosol caused a decrease of both spontaneous and evoked norepinephrine release, indicating that it affects pre-existing plasma membrane-associated norepinephrine transporter, rather than the incorporation of novel norepinephrine transporter molecules into the plasma membrane.


CONCLUSIONS
Hydroxytyrosol potently enhances norepinephrine transporter activity in pheochromocytoma PC12 cells, suggesting that combinatorial therapy employing hydroxytyrosol may improve the effectiveness of (131)I-MIBG as a diagnosis and treatment modality.
Luzón-Toro
Berta
B
Institute of Parasitology and Biomedicine "López-Neyra", Spanish National Research Council (CSIC), 18100 Granada, Spain.
Geerlings
Arjan
A
Hilfiker
Sabine
S
D019797:3-Iodobenzylguanidine; D000818:Animals; D009638:Norepinephrine / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D014316:Tritium
D050484:Norepinephrine Plasma Membrane Transport Proteins; D014316:Tritium; C005975:3,4-dihydroxyphenylethanol; D019797:3-Iodobenzylguanidine; D010626:Phenylethyl Alcohol; D009638:Norepinephrine