monensin and Adrenal-Cortex-Neoplasms

Possible involvement of cell membrane ion transport systems in the uptake and extrusion of Tc-99m-MIBI was investigated by using various buffers with or without Na+ and Ca++, and ion transport inhibitors in a tumor cell line. The ion transport modulators dimethyl amiloride (DMA), verapamil, flunarizine and monensin were used. The uptake of Tc-99m-MIBI was significantly increased in all buffers containing either Na+ or Ca++ alone or none of them. There was significantly increased uptake of Tc-99m-MIBI especially in buffers without Na+. Verapamil, a L-type Ca++ channel blocker, increased Tc-99m-MIBI uptake in all buffers. Flunarizine, which inhibits Na+/ Ca++ channels, caused significantly increased accumulation of Tc-99m-MIBI only in buffer containing both Na+ and Ca++. Monensin, a sodium ionophore, significantly increased uptake of Tc-99m-MIBI. DMA, a potent Na+/H+ antiport inhibitor, significantly inhibited the uptake of Tc-99m-MIBI in all buffers. In conclusion, Tc-99m-MIBI behaves like Na+ during its uptake and extrusion. Extrusion of Tc-99m-MIBI may involve both verapamil- and flunarizine-sensitive pathways.

Topics: Adrenal Cortex Neoplasms; Amiloride; Calcium; Calcium Channel Blockers; Calcium Channels; Carcinoma, Small Cell; Flunarizine; Humans; Monensin; Sodium; Sodium Channels; Technetium Tc 99m Sestamibi; Tumor Cells, Cultured; Verapamil

Topics: Adrenal Cortex Neoplasms; Adrenocorticotropic Hormone; Animals; Bucladesine; Mice; Monensin; Nigericin; Steroids

We have previously described in rats the selective uptake of HDL-associated cholesterol esters (traced by [3H]cholesteryl oleyl ether) in excess of the uptake of HDL-associated apoA-I. In the present studies we show that the mechanism also exists in cultured cells of human and mouse origin as well. This selective uptake represents a net uptake of cholesterol esters and not an isotope exchange, as shown by mass flux studies in adrenal cells. Inhibitors of receptor recycling, chloroquine, monensin, and colchicine, inhibited uptake of apoA-I from HDL by Hep G-2 human hepatoma cells to about the same extent as a reference protein, asialofetuin, but inhibited uptake of the cholesteryl ether tracer much less. Levels of NaN3 which effectively inhibited sucrose pinocytosis inhibited uptake of apoA-I to about the same extent but did not inhibit uptake of the cholesteryl ether at all. Thus, not only receptor recycling, but endocytosis as well, appears not to be involved in selective uptake. This conclusion was supported by studies in which synthetic HDL particles were made to contain two neutral lipid core tracers; one of them, the [3H]cholesteryl ether previously used, was selectively taken up, whereas the other, [14C]sucrose octaoleate, was excluded from selective uptake. Thus, selective uptake cannot involve endocytosis of the entire lipid core, but may involve other specific transfer mechanisms.

Topics: Adrenal Cortex Neoplasms; alpha-Fetoproteins; Animals; Apolipoprotein A-I; Apolipoproteins A; Asialoglycoproteins; Azides; Cells, Cultured; Chloroquine; Cholesterol; Cholesterol Esters; Colchicine; Fetuins; Fibroblasts; Heparin; Humans; Kinetics; Lipoproteins, HDL; Lipoproteins, LDL; Liver Neoplasms; Mice; Monensin; Pinocytosis; Rats; Sodium Azide