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- W4210270419 abstract "Using [125I]RTI-55 to label the dopamine transporter (DAT), our laboratory has consistently detected one binding site as well as one component of [3H]DA uptake. We report here the identification of a novel partial inhibitor of [3H]DA uptake and DAT binding (SoRI-9804). [125I]RTI-55 binding to the DAT (mouse caudate, rat caudate, HEK cells expressing the cloned DAT), the 5-HT transporter (rat brain), and [3H]DA uptake (rat caudate synaptosomes) were conducted using published procedures. 4-[(Diphenylmethyl)amino]-2-phenylquinazoline (SoRI-9804) was essentially inactive at SERT binding and resolved two DAT binding components in all three tissues, having high affinity (mean Ki of 465 nM) for about 40% of the binding sites and an essentially immeasurable Ki (> 100 μM) for the remaining 60% of the binding sites. The [3H]DA uptake experiments indicated that about 50% of uptake was SoRI-9804-sensitive. Saturation binding experiments showed that SoRI-9804 competitively inhibited [125I]RTI-55 binding to the SoRI-9804-sensitive binding component. To determine if the two binding sites discriminated by SoRI-9804 were regulated by the MAP kinase pathway, rat caudate synaptosomes were incubated in the absence or presence of 10 μM of PD98059, which inhibits activation of the MAP kinase pathway. The results indicated that inhibition of MAPK/ERK kinase decreased the total Bmax of the DAT by 90%. Treatment with PD98059 increased the proportion of the SoRI-9804-sensitive binding component from 68–80% of the total Bmax. The PD98059 experiments suggest that inhibition of MAP kinase cannot explain the differential interaction of SoRI-9804 with the DAT. Viewed collectively, the present results indicate that SoRI-9804 discriminates two components of the DA transporter. Further studies will be needed to determine the underlying mechanism of this effect and if partial inhibition of DA uptake results in any unique behavioral effects. Synapse 43:268–274, 2002. © 2002 Wiley-Liss, Inc." @default.
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- W4210270419 date "2002-03-01" @default.
- W4210270419 modified "2023-09-27" @default.
- W4210270419 title "Synthesis and characterization of biodegradable poly(ε-caprolactone urethane(s). I. Effects of the polyol molecular weight, catalyst, and chain extender on the molecular and physical characteristics" @default.
- W4210270419 doi "https://doi.org/10.1002/syn.10046.abs" @default.
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