Mechanisms of uptake of norepinephrine (NE) and Meta-iodobenzylguanidine (MIBG) into cultured bovine adrenomedullary cells: Evidence for uptake-one

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

OSTI ID:6640373

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

The nature of the sodium-dependent and sodium-independent uptake systems for NE and MIBG were studied in cultured bovine adrenomedullary cells, a model system exhibiting uptake mechanisms analogous to those in human pheochromocytomas. At concentrations less than or equal to1.0..mu..M, uptake of NE and MIBG was primarily by the sodium-dependent system; at higher concentrations, greater than or equal to 20 ..mu..M, uptake of both agents was predominantly by the sodium-independent pathway. Desmethylimipramine (DMI) inhibited the sodium-dependent uptake of 0.5 and 20.0 ..mu..M NE (IC-50 = 0.05 and 1.0 ..mu..M, respectively) and the sodium-dependent uptake of 0.5 ..mu..M MIBG(IC-50 of 0.05 ..mu..M). However, at 0.5 and 20 ..mu..M, NE and MIBG, the sodium-independent uptake was 100 to 1000 fold less sensitive to the inhibitory effects of DMI. Cocaine, an Uptake-one inhibitor structurally unrelated to DMI, inhibited the sodium-dependent and independent NE and MIBG uptake in a pattern similar to DMI. DMI was a competitive inhibitor of sodium-dependent NE and MIBG uptake but not of sodium-independent uptake. Similarly, NE and MIBG were competitive inhibitors of each other when uptake occurred by the sodium-dependent pathway but not when uptake occurred by the sodium-independent pathway. The sodium-dependent pathway is a saturable, energy-dependent system which is inhibited by classical Uptake-one inhibitors. The sodium-independent uptake system may represent a diffusion mechanism. Consistent with these in vitro results, scintiscans of pheochromocytomas with (I-131)MIBG have been altered in vivo by DMI-like drugs and, therefore, appear to reflect Uptake-one.

• Research Organization: Univ. of Michigan Medical Center, Ann Arbor, MI
• OSTI ID: 6640373
• 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
ADRENAL GLANDS
ADRENAL HORMONES
ALKALI METALS
ALKALOIDS
AMINES
ANESTHETICS
ANIMAL CELLS
ANTIDEPRESSANTS
AUTONOMIC NERVOUS SYSTEM
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL PATHWAYS
BODY
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CULTURES
CENTRAL NERVOUS SYSTEM AGENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
COCAINE
DISEASES
DRUGS
ELEMENTS
ENDOCRINE GLANDS
ENZYME INHIBITORS
GLANDS
HETEROCYCLIC COMPOUNDS
HORMONES
IMIPRAMINE
IN VITRO
INHIBITION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MEMBRANE TRANSPORT
METALS
MIBG
NEOPLASMS
NERVOUS SYSTEM
NEUROREGULATORS
NORADRENALINE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PSYCHOTROPIC DRUGS
RADIOPHARMACEUTICALS
REACTION KINETICS
SENSITIVITY
SODIUM
STEROID HORMONES
SYMPATHOMIMETICS
TRACER TECHNIQUES
TUMOR CELLS
UPTAKE