期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1983
卷号：80
期号：2
页码：584-588
DOI：10.1073/pnas.80.2.584
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：[2-3H]Dihydrotetrabenazine (2-hydroxy-3-isobutyl-9, 10-dimethoxy-1,2,3,4,6,7-hexahydro-11b-H-benzo [a]-quinolizine), a derivative of the neuroleptic tetrabenazine, binds to the membrane of purified bovine chromaffin granules. Specific binding was characterized by Kd and Bmax values of 3.1 nM and 62 pmol/mg of membrane protein, respectively. It was reversible, with association and dissociation rate constants of 0.22 x 10(6) M-1 s-1 and 1.8 x 10(-3) s-1, respectively. Binding sites were present in extracts of medulla but not in corticoadrenal extracts; in the medulla they were restricted to chromaffin granule membranes, [2-3H]Dihydrotetrabenazine binding occurred on the catecholamine carrier of the chromaffin granule membrane because it was clearly correlated with inhibition of norepinephrine uptake. In addition, inhibitors and substrates of the uptake reaction displaced [2-3H]dihydrotetrabenazine from its binding sites, and their potency as displacers was qualitatively correlated with their IC50 or Km. These results suggest that use of [2-3H]dihydrotetrabenazine binding might be an interesting technique in the study of the vesicular monoamine carrier.
