TY - JOUR
T1 - RELEASE MECHANISMS OF {[I-125]METAIODOBENZYLGUANIDINE IN NEUROBLASTOMA-CELLS - EVIDENCE OF A CARRIER-MEDIATED EFFLUX}
AU - Servidei, Tiziana
AU - Iavarone, A.
AU - Lasorella, A.
AU - Mastrangelo, Stefano
AU - Riccardi, Riccardo
PY - 1995
Y1 - 1995
N2 - {[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.}
AB - {[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.}
KW - CARRIER-MEDIATED}
KW - CELL LINES
KW - EFFLUX
KW - NEUROBLASTOMA
KW - RELEASE, NEUROTRANSMITTER
KW - {[I-131] METAIODOBENZYLGUANIDINE ([I-131]MIBG)
KW - CARRIER-MEDIATED}
KW - CELL LINES
KW - EFFLUX
KW - NEUROBLASTOMA
KW - RELEASE, NEUROTRANSMITTER
KW - {[I-131] METAIODOBENZYLGUANIDINE ([I-131]MIBG)
UR - http://hdl.handle.net/10807/16319
U2 - 10.1016/0959-8049(95)00042-H
DO - 10.1016/0959-8049(95)00042-H
M3 - Article
SN - 0959-8049
VL - 31A
SP - 591
EP - 595
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -