EXPRESSION OF THE EXTRANEURONAL MONOAMINE TRANSPORTER (UPTAKE(2)) IN HUMAN GLIOMA-CELLS

Tritiated methylphenylpyridinium ([H-3]MPP(+)), a substrate of the neu ronal and extraneuronal noradrenaline transporter (uptake(1) and uptak e(2), respectively) and of the organic cation transporter (OCT1), was used to characterize the amine transport system of the established hum an glioma cell line SK-MG-1. Uptake of [H-3]MPP(+) (35 nM) into SK-MG- 1 cells increased linearly with time for up to 15 min. Selective uptak e(1) inhibitors (e.g. (+)oxaprotiline) or omission of Na+ or Cl- ions did not affect [H-3]MPP(+) uptake, whereas uptake, inhibitors such as O-methyl-isoprenaline (OMI) or corticosterone as well as depolarizing concentrations of K+ or Ba2+ strongly reduced [H-3]MPP(+) uptake. Init ial rates of OMI(100 mu M)-sensitive [H-3]MPP(+) uptake were saturable , with a K-m of about 17 mu M and a maximal rate of about 50 pmol/ (mi n x mg protein). IC50 (or K-i) values for inhibition of [H-3]MPP(+) up take by substrates and inhibitors of uptake, or OCT1 were highly signi ficantly correlated with published IC50 values for inhibition of uptak e, but not with corresponding values for inhibition of OCT1. The resul ts presented here clearly demonstrate that human glioma cells express an uptake, transporter. Thus, glial cells in the human central nervous system endowed with this transporter are likely to contribute to the inactivation of neuronally released noradrenaline.