Comparison of the pharmacological properties of cloned rat, human, and bovine norepinephrine transporters

The aims of this study were to characterize the recently cloned rat norepin ephrine transporter (NET) in more detail and in particular to study possibl e species differences in its pharmacological properties compared with the h uman and bovine NETs. The study was carried out by measuring the uptake of [H-3]norepinephrine in COS-7 cells expressing the NET after transient trans fection with rat, human, or bovine NET cDNA. There were small but significa nt differences between the rat NET and the human or bovine NETs with respec t to the affinities of sodium ions (greater for rat than for bovine) of the substrates norepinephrine, epinephrine, and 1-methyl-4-phenylpyridinium (g reater for human than for rat), and of the inhibitor cocaine (greater for h uman and bovine than for rat), whereas the affinities of dopamine and of mo st inhibitors, including tricyclic antidepressants, showed no species diffe rences. The fact that the affinities for some substrates, cocaine and sodiu m ions exhibited small but significant interspecies differences among the r at, human, and bovine NETs suggests that ligand recognition, the translocat ion process, and sodium ion dependence are influenced differentially by jus t 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 ex trapolated, in all except the most quantitative analyses, to the properties of the human NET.