Extraneuronal noradrenaline transport (uptake2) in a human cell line (Caki-1 cells).
This study describes for the first time an experimental system for the extraneuronal transport mechanism of noradrenaline (uptake 2) which is based on a clonal cell line (Caki-1). Caki-1 cells were originally derived from a human renal cell carcinoma. The conclusion that these cells express uptake 2 is supported by several experimental findings. (1) The initial rate of 3H-noradrenaline uptake in Caki-1 cells is saturable, the Km being 450 mumol/l. (2) Inhibitors of uptake 2 such as corticosterone (1 mumol/l) and O-methyl-isoprenaline (100 mumol/l) largely inhibit 3H-noradrenaline uptake in Caki-1 cells. Whereas inhibitors of the neuronal transport mechanism for noradrenaline (uptake 1) such as desipramine (1 mumol/l) and cocaine (10 mumol/l) do not reduce it. (3) Depolarization of Caki-1 cells by the elevation of extracellular potassium inhibits 3H-noradrenaline uptake. (4) There is a highly significant correlation between the Ic50's of various compounds for the inhibition of 3H-noradrenaline uptake in Caki-1 cells and rabbit aorta known to possess uptake2. Interestingly enough, uptake 2 in Caki-1 cells and rabbit aorta is inhibited by cimetidine, quinidine and procainamide which are substrates of the renal transport mechanism for organic cations. Moreover, 3H-cimetidine is shown to be a substrate of uptake 2 in the isolated perfused rat heart. These results indicate a striking similarity between uptake 2 and the renal transport mechanism for organic cations.
Schömig
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Institut für Pharmakologie und Toxikologie, Universität Würzburg, Federal Republic of Germany.
Schönfeld
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D000818:Animals; D002478:Cells, Cultured; D002927:Cimetidine / Q000493:pharmacokinetics; D003345:Corticosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism*; D006801:Humans; D007545:Isoproterenol / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000493:pharmacokinetics*; D009994:Osmolar Concentration; D010477:Perfusion; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D014316:Tritium
D014316:Tritium; C008401:metiprenaline; D002927:Cimetidine; D012964:Sodium; D007545:Isoproterenol; D003345:Corticosterone; D009638:Norepinephrine; D011224:Prazosin