Active uptake and extravesicular storage of m-iodobenzylguanidine in human neuroblastoma SK-N-SH cells

Radio-iodinated m-iodobenzylguanidine (MIBG), an analogue of the neurotransmitter norepinephrine (NE), is increasingly used in the diagnosis and treatment of neural crest tumors. Active uptake and subsequent retention of MIBG and NE was studied in human neuroblastoma SK-N-SH cells. Neuron-specific u...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1989-06, Vol.49 (11), p.2941-2944
Main Authors: SMETS, L. A, LOESBERG, C, JANSSEN, M, METWALLY, E. A, HUISKAMP, R
Format: Article
Language:English
Subjects:
3-Iodobenzylguanidine
Antineoplastic agents
Biological and medical sciences
General aspects
Humans
Imipramine - pharmacology
Iodine Radioisotopes - pharmacokinetics
Iodobenzenes - pharmacokinetics
m-iodobenzylguanidine
Medical sciences
Neuroblastoma - metabolism
norepinephrine
Norepinephrine - pharmacokinetics
Pharmacology. Drug treatments
Reserpine - pharmacology
Time Factors
Tumor Cells, Cultured - metabolism
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Radio-iodinated m-iodobenzylguanidine (MIBG), an analogue of the neurotransmitter norepinephrine (NE), is increasingly used in the diagnosis and treatment of neural crest tumors. Active uptake and subsequent retention of MIBG and NE was studied in human neuroblastoma SK-N-SH cells. Neuron-specific uptake of [125I]MIBG and [3H]NE saturated at extracellular concentration of 10(-6) M and exceeded by 20-30-fold that by passive diffusion alone. A minimum of 50% of accumulated MIBG remained permanently stored but the SK-N-SH cells were incapable of retaining recaptured [3H]NE. [125I]MIBG was displaced from intracellular binding sites by unlabeled MIBG with 10-fold higher potency than by unlabeled NE. MIBG stored in SK-N-SH cells was insensitive to depletion by the inhibitor of granular uptake reserpine (RSP) and was not precipitated in a granular fraction by differential centrifugation. Only few electron-dense granules were found in these cells by electron microscopy. In contrast, MIBG storage in PC-12 pheochromocytoma cells which contained many storage granules, was sensitive to RSP and part of accumulated drug was recovered in a granular fraction. Accordingly, storage of MIBG in the SK-N-SH neuroblastoma cells is predominantly extravesicular and thus essentially different from that of biogenic amines in normal adrenomedullary tissue or in pheochromocytoma tumors, while sharing with these tissues a common mechanism of active uptake.
ISSN:0008-5472
1538-7445