Effect of Uptake-one inhibitors on the uptake of norepinephrine and metaiodobenzylguanidine
The mechanisms underlying the uptake of the radiopharmaceutical metaiodobenzylguanidine (MIBG) and the catecholamine norepinephrine (NE) were studied using cultured bovine adrenomedullary cells as an in vitro model system. Sodium-dependent and sodium-independent uptake systems have been identified and characterized for both MIBG and NE. The sodium-dependent uptake of Ne and MIBG was inhibited by the selective Uptake-one inhibitors, desmethylimipramine (DMI) and cocaine, whereas the sodium-independent uptake for NE and MIBG was much less sensitive to inhibition by these agents. The sodium-dependent uptake system fulfills the criteria for the neuronal Uptake-one system, and the sodium-independent uptake system fulfills the criteria for a passive diffusion mechanism. Arterial concentrations proximal to the dog adrenal were very small suggesting that the sodium-dependent (Uptake-one) system is predominant in vivo. Consistent with the in vitro observations, the in vivo uptake of MIBG and NE into dog adrenal medullae was effectively blocked by pretreatment with DMI or cocaine. Therefore, iodine-131 MIBG scintigraphy of the adrenal appears to reflect uptake by way of the Uptake-one system.
- Research Organization:
- Univ. of Michigan, Ann Arbor
- OSTI ID:
- 5270266
- Journal Information:
- J. Nucl. Med.; (United States), Vol. 26:8
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ADRENAL GLANDS
SCINTISCANNING
DIFFUSION
INHIBITION
GUANIDINES
UPTAKE
MEMBRANE TRANSPORT
NORADRENALINE
RADIOPHARMACEUTICALS
CHEMICAL PROPERTIES
AMINES
ANIMAL CELLS
COCAINE
DOGS
IMIPRAMINE
IN VITRO
IODINE 131
SODIUM COMPOUNDS
ADRENAL HORMONES
ALKALI METAL COMPOUNDS
ALKALOIDS
ANESTHETICS
ANIMALS
ANTIDEPRESSANTS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBONIC ACID DERIVATIVES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM AGENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
COUNTING TECHNIQUES
DAYS LIVING RADIOISOTOPES
DIAGNOSTIC TECHNIQUES
DRUGS
ENDOCRINE GLANDS
GLANDS
HETEROCYCLIC COMPOUNDS
HORMONES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PSYCHOTROPIC DRUGS
RADIOISOTOPE SCANNING
RADIOISOTOPES
STEROID HORMONES
SYMPATHOMIMETICS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques