Mechanisms of uptake of norepinephrine (NE) and meta-iodobenzylguanidines (MIBG) into cultured human pheochromocytoma cells

Conference · Sun Jan 01 04:00:00 EST 1984 · J. Nucl. Med.; (United States)

OSTI ID:6640381

Jaques, S Jr; Tobes, M C; Sisson, J C; Baker, J A

(I-131)MIBG concentrates into human pheochromocytomas. The uptake of MIBG is thought to parallel that of NE. The authors have evaluated this relationship using (H-3)NE and (I-131) or (I-125)MIBG in primary cultures of human pheochromocytomas (pheos), age 4 to 10 days, obtained from 11 patients. Both NE and MIBG were taken up by temperature-dependent mechanisms. The rate of uptake of either agent was not correlated with cell catecholamine content suggesting that the uptake mechanism was not related to the catecholamine storage or synthetic capacity of the cells. Competitive inhibition studies suggested that at least one and possibly two uptake mechanism(s) for both agents existed. In fact, two potentially shared uptake systems/mechanisms were identified: a sodium-dependent and a sodium-independent pathway. The sodium-dependent system was characterized by high affinity, low capacity, saturability and ouabain-sensitivity. NE and MIBG were also taken up by a temperature-dependent, sodium-independent, ouabain-insensitive system which was apparently unsaturable. Although the rate of uptake (pmols/10/sup 6/ cells/ 10 min) for both agents at 1.0 ..mu..M varied considerably (0.19 to 46.17 for NE and 0.24 to 71.37 for MIBG), the ratio (1.58:1) of the rate of MIBG to NE uptake was conserved (r = 0.97). The variable uptake observed in vitro suggests that human pheochromacytomas possess, in variable proportions, sodium-dependent and sodium-independent uptake systems for NE and MIBG. Scintigraphic portrayal of pheos in vivo appears to reflect (I-131)MIBG uptake by the sodium-dependent system.

• Research Organization: Univ. of Michigan Medical Center, Ann Arbor, MI
• OSTI ID: 6640381
• Report Number(s): CONF-840619-
• Conference Information: Journal Name: J. Nucl. Med.; (United States) Journal Volume: 25:5
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ADRENAL HORMONES
ALKALI METALS
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CULTURES
DAYS LIVING RADIOISOTOPES
DIAGNOSTIC USES
DISEASES
DRUGS
DUAL-ISOTOPE SUBTRACTION TECHNIQUE
ELECTRON CAPTURE RADIOISOTOPES
ELEMENTS
HORMONES
IN VITRO
IN VIVO
INHIBITION
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE 131
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
MAMMALS
MAN
MEMBRANE PROTEINS
MEMBRANE TRANSPORT
METALS
MIBG
NEOPLASMS
NERVOUS SYSTEM
NEUROREGULATORS
NORADRENALINE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PRIMATES
PROTEINS
RADIOISOTOPES
RADIOPHARMACEUTICALS
REACTION KINETICS
RECEPTORS
SODIUM
STEROID HORMONES
SYMPATHOMIMETICS
TEMPERATURE DEPENDENCE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUMOR CELLS
UPTAKE
USES
VERTEBRATES