The transport of (+)-amphetamine by the neuronal noradrenaline carrier.
PC-12 cells (a clonal line of rat phaeochromocytoma cells) take up noradrenaline by a transport system which is identical with the neuronal amine transport system ("uptake1"). The uptake of 3H-noradrenaline into reserpine-pretreated PC-12 cells (monoamine oxidase inhibited) was saturable (Km = 0.6 +/- 0.1 mumol/l), dependent on sodium and chloride, and competitively inhibited by (+)-amphetamine (Ki = 0.18 +/- 0.04 mumol/l), cocaine (Ki = 0.55 +/- 0.15 mumol/l) and desipramine (Ki = 4.3 +/- 0.6 nmol/l). The uptake and accumulation of 3H (+)-amphetamine showed characteristics comparable to those of 3H-noradrenaline, since the uptake of 3H (+)-amphetamine (0.1 mumol/l) was reduced by omission of sodium or chloride from the incubation medium. The sodium-sensitive component of uptake and accumulation of 3H (+)-amphetamine was fully inhibited by cocaine and desipramine. The IC50 of desipramine for inhibition of the sodium-sensitive component of the 1-min uptake of 3H (+)-amphetamine (20 nmol/l) was about 2 nmol/l, i.e., identical with the Ki for inhibition of uptake of 3H-noradrenaline. At concentrations above 1 mumol/l, desipramine additionally caused an inhibition of the sodium-independent permeation of 3H (+)-amphetamine into PC-12 cells. Hence, by using a homogeneous population of cells endowed with "uptake1", it is possible to demonstrate - besides a pronounced lipophilic entry - a carrier-mediated uptake of 3H (+)-amphetamine.
D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D003042:Cocaine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D003913:Dextroamphetamine / Q000378:metabolism*; D007700:Kinetics; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010673:Pheochromocytoma / Q000378:metabolism; D051381:Rats
D003042:Cocaine; D003891:Desipramine; D003913:Dextroamphetamine; D009638:Norepinephrine