Effects of ion channel modulators in the influx and efflux of Tc-99m-MIBI.
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.
Arbab
A S
AS
Department of Radiology, Yamanashi Medical University, Yamanashi, Japan. saali@res.yamanashi-med.ac.jp
Koizumi
K
K
Toyama
K
K
Arai
T
T
Araki
T
T
D000306:Adrenal Cortex Neoplasms / Q000378:metabolism; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000378:metabolism; D005444:Flunarizine / Q000494:pharmacology; D006801:Humans; D008985:Monensin / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D017256:Technetium Tc 99m Sestamibi / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D015222:Sodium Channels; C039465:5-dimethylamiloride; D000584:Amiloride; D008985:Monensin; D017256:Technetium Tc 99m Sestamibi; D012964:Sodium; D014700:Verapamil; D005444:Flunarizine; D002118:Calcium