TY - JOUR T1 - Comparison of the Pharmacological Properties of Cloned Rat, Human, and Bovine Norepinephrine Transporters JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 761 LP - 767 VL - 290 IS - 2 AU - Filip A. Paczkowski AU - Lesley J. Bryan-Lluka AU - Peter Pörzgen AU - Michael Brüss AU - Heinz Bönisch Y1 - 1999/08/01 UR - http://jpet.aspetjournals.org/content/290/2/761.abstract N2 - The aims of this study were to characterize the recently cloned rat norepinephrine transporter (NET) in more detail and in particular to study possible species differences in its pharmacological properties compared with the human and bovine NETs. The study was carried out by measuring the uptake of [3H]norepinephrine in COS-7 cells expressing the NET after transient transfection with rat, human, or bovine NET cDNA. There were small but significant differences between the rat NET and the human or bovine NETs with respect to the affinities of sodium ions (greater for rat than for bovine) of the substrates norepinephrine, epinephrine, and 1-methyl-4-phenylpyridinium (greater for human than for rat), and of the inhibitor cocaine (greater for human and bovine than for rat), whereas the affinities of dopamine and of most inhibitors, including tricyclic antidepressants, showed no species differences. The fact that the affinities for some substrates, cocaine and sodium ions exhibited small but significant interspecies differences among the rat, human, and bovine NETs suggests that ligand recognition, the translocation process, and sodium ion dependence are influenced differentially by just a few amino acid exchanges in the primary sequences of the transporters. On the other hand, the lack of any major differences in the pharmacological properties of the rat, human, and bovine NETs in this study suggests that data obtained in previous studies on rat tissues and bovine cells can be extrapolated, in all except the most quantitative analyses, to the properties of the human NET. The American Society for Pharmacology and Experimental Therapeutics ER -