EFFECT OF UPTAKE-ONE INHIBITORS ON THE UPTAKE OF NOREPINEPHRINE AND METAIODOBENZYLGUANIDINE

  • 1 January 1985
    • journal article
    • research article
    • Vol. 26  (8) , 897-907
Abstract
The mechanisms underlying the uptake of the radiopharmaceutical metaiodobenzylguanidine (MIBG) and the catecholamine norepinephrine (NE) were sutided using cultured bovine adrenomedullary cells as an in vitro model system. Na-dependent and Na-independent uptake systems were identified and characterized for both MIBG and NE. The Na-dependent uptake of NE and MIBG was inhibited by the selective uptake-one inhibitors, demethylimipramine (DMI) and cocaine, whereas the Na-independent uptake for NE and MIBG was much less sensitive to inhibition by these agents. The Na-dependent uptake system fulfills the critieria for the neuronal Uptake-one system, and the Na-independent uptake system fulfills the criteria for a passive diffusion mechanism. Both NE and MIBG were transported into cultured bovine adrenomedullary cells by both uptake systems; the relative role of each uptake system was dependent upon the concentration of NE and MIBG in the media. Arterial concentrations proximal to the dog adrenal were very small suggesting that the Na-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, 131I MIBG scintigraphy of the adrenal appears to reflect uptake by way of the Uptake-one system.