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Effect of Uptake-one inhibitors on the uptake of norepinephrine and metaiodobenzylguanidine

Journal Article · · J. Nucl. Med.; (United States)
OSTI ID:5270266
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), Journal Name: J. Nucl. Med.; (United States) Vol. 26:8; ISSN JNMEA
Country of Publication:
United States
Language:
English

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