INHIBITION OF STRIATAL DOPAMINE TRANSPORTER ACTIVITY BY 17-BETA-ESTRADIOL

Striatal synaptosomes from ovariectomized rats were prepared to examin e the effect of 17 beta-estradiol on [H-3]dopamine uptake. Estradiol i nhibited [H-3]dopamine uptake in a dose-dependent manner, with an IC50 of 7.3 mu M. Use of identical concentrations of progesterone had no e ffect on [H-3]dopamine uptake. The effects of estradiol were exerted b y decreasing the affinity of the transporter for dopamine, as revealed by a dose-dependent increase in the K-m. The K-m values for 0 (contro l), 10, and 100 mu M estradiol were 108 +/- 11, 258 +/- 44 and 415 +/- 40 nM, respectively, with each of the three concentrations tested bei ng significantly different among each other. No statistically signific ant differences were obtained for the V-max, with values for the three increasing doses being 9.2 +/- 0.8, 8.3 +/- 0.5 and 7.3 +/- 0.8 pmol/ min per mg protein. These results demonstrate that estradiol, but not progesterone, inhibits striatal dopamine uptake by decreasing the affi nity of the transporter fur dopamine. Such a mechanism may serve as on e of the bases for the modulatory effects of estradiol upon the nigros triatal dopaminergic system. (C) 1998 Elsevier Science B.V.