Comparison of the sodium dependency of uptake of meta-lodobenzylguanidine and norepinephrine into cultured bovine adrenomedullary cells

Journal Article · Thu Nov 01 04:00:00 EST 1984 · Mol. Pharmacol.; (United States)

OSTI ID:5969562

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

Radioiodinated meta-iodobenzylguanidine (MIBG), a scintigraphic agent used for the detection of human pheochromocytomas, is thought to utilize the same uptake and retention mechanism(s) as norepinephrine (NE). Using cultured bovine adrenomedullary cells, the authors compared the mechanism(s) of uptake of MIBG to that of NE. Two different uptake systems were identified. NE and MIBG were taken up by a sodium-dependent system that was characterized by: 1) temperature dependency; 2) high affinity: Km of 1.22 +/- 0.12 microM for MIBG and 1.41 +/- 0.50 microM for NE; 3) low capacity: Vm (picomoles/10(6) cells/10 min) of 64.3 +/- 3.3 for MIBG and 36.6 +/- 7.2 for NE; 4) saturability; 5) ouabain sensitivity; and 6) energy dependency. However, NE and MIBG also were taken up by a temperature-dependent, sodium-independent, apparently unsaturable, and energy-independent system. The sodium-dependent uptake system fulfills many of the criteria for Uptake1 whereas the sodium-independent uptake system is most likely a passive diffusion process. NE uptake proceeded predominantly by the sodium-dependent process. Uptake of MIBG occurred by both pathways at low concentrations, but at high concentrations (greater than 10 microM) uptake was predominantly (75 to 100%) by the sodium-independent process. Inhibition studies suggest that MIBG and NE are transported by the same carrier involved in the sodium-dependent system. Scintiscans of the human adrenals and pheochromocytomas appear to reflect uptake of (/sup 131/I)MIBG by the sodium-dependent system.

• Research Organization: Univ. of Michigan Medical Center, Ann Arbor
• OSTI ID: 5969562
• Journal Information: Mol. Pharmacol.; (United States), Journal Name: Mol. Pharmacol.; (United States) Vol. 26:3; ISSN MOPMA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ADRENAL GLANDS
ADRENAL HORMONES
ALKALI METALS
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOLOGICAL PATHWAYS
BODY
CARDIOTONICS
CARDIOVASCULAR AGENTS
CATTLE
CELL CULTURES
COUNTING TECHNIQUES
DIAGNOSIS
DIAGNOSTIC TECHNIQUES
DISEASES
DOMESTIC ANIMALS
DRUGS
ELEMENTS
ENDOCRINE GLANDS
GLANDS
HORMONES
IODINE ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
METALS
NEOPLASMS
NEUROREGULATORS
NORADRENALINE
ORGANS
RADIOISOTOPE SCANNING
RADIOPHARMACEUTICALS
RESPONSE MODIFYING FACTORS
RETENTION
RUMINANTS
SCINTISCANNING
SODIUM
STEROID HORMONES
SYMPATHOMIMETICS
UPTAKE
VERTEBRATES