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Hydroxytyrosol increases norepinephrine transporter function in pheochromocytoma cells.

AbstractINTRODUCTION:
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.
CONCLUSION:
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.
AuthorsBerta Luzón-Toro, Arjan Geerlings, Sabine Hilfiker
JournalNuclear medicine and biology (Nucl Med Biol) Vol. 35 Issue 7 Pg. 801-4 (Oct 2008) ISSN: 0969-8051 [Print] United States
PMID18848665 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Norepinephrine Plasma Membrane Transport Proteins
  • Tritium
  • 3,4-dihydroxyphenylethanol
  • 3-Iodobenzylguanidine
  • Phenylethyl Alcohol
  • Norepinephrine
Topics
  • 3-Iodobenzylguanidine
  • Animals
  • Norepinephrine (metabolism)
  • Norepinephrine Plasma Membrane Transport Proteins (drug effects, physiology)
  • PC12 Cells
  • Phenylethyl Alcohol (analogs & derivatives, pharmacology)
  • Rats
  • Tritium

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