RELEASE MECHANISMS OF {[I-125]METAIODOBENZYLGUANIDINE IN NEUROBLASTOMA-CELLS - EVIDENCE OF A CARRIER-MEDIATED EFFLUX}

Stefano Mastrangelo, Tiziana Servidei, Riccardo Riccardi, A Iavarone, A Lasorella

Risultato della ricerca: Contributo in rivistaArticolo in rivista

10 Citazioni (Scopus)

Abstract

{[I-131]metaiodobenzylguanidine ([I-131]MIBG) is selectively taken up and stored by tumours derived from the neural crest, and is used for diagnosis and treatment of neuroblastoma (NB). The antitumoral effect of [I-131]MIBG is closely related to the intracellular level of the radiopharmaceutical compound, which is dependent on uptake and storage/release mechanisms. While MIBG uptake is well characterised, storage and release mechanisms are still controversial. In order to better characterise [I-125]MIBG release mechanisms, we studied the basal and stimulated efflux of [I-125]MIBG in the human NE cell line, SH-SY5Y, preloaded with 0.1 mu M [I-125]MIBG for 1 h. We found that [I-125]MIBG basal efflux is highly temperature-dependent, that [I-125]MIBG release, induced by cell depolarisatlon with high potassium, is mainly calcium-independent, and induced by exchange with cold MIBG or noradrenaline, inversion of the sodium gradient across the cell membrane by veratridine or by substitution of sodium chloride with equimolar concentration of lithium chloride. The exposure of NE cells to imipramine, an Uptake-1 inhibitor, also produces a net stimulatory effect on [I-125]MIBG release. However, when used in association with other releasing stimuli, such as higher levels of intracellular sodium or external agonists, imipramine abolishes the consequent increase of [I-125]MIBG release. Our findings suggest that stimulated [I-125]MIBG release is mediated by a carrier, most probably the uptake carrier working in a reverse mode, while a minimal fraction of[I-125]MIBG is released by an exocytotic mechanism.}
Lingua originaleEnglish
pagine (da-a)591-595
Numero di pagine5
RivistaEuropean Journal of Cancer
Volume31A
DOI
Stato di pubblicazionePubblicato - 1995

Keywords

  • CARRIER-MEDIATED}
  • CELL LINES
  • EFFLUX
  • NEUROBLASTOMA
  • RELEASE, NEUROTRANSMITTER
  • {[I-131] METAIODOBENZYLGUANIDINE ([I-131]MIBG)

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