Summary
Biochemical and pharmacological studies suggest that the binding of [3H]mazindol is functionally related to the dopamine uptake carrier complex in rodent striatum. In order to study further the relationship between the substrate recognition site for dopamine uptake and the high-affinity binding site for mazindol the uptake of [3H]dopamine and the binding of [3H]mazindol was studied in BALB/cBy mouse striatum in various buffers (Tris, HEPES, bicarbonate-phosphate). Kinetic analysis showed that theK d, of the binding of [3H]mazindol and theK m of the uptake of [3Mdopamine was changed by different sodium concentrations and/or by the presence of Tris, while theB max, and theV max remained essentially the same. However, the shape of the Na+ dependency curves was not the same for mazindol binding and dopamine uptake in the various buffers. The inhibitory effect of other cations such as K+ and Tris was also different on binding and uptake under similar experimental circumstances. Dopamine did not slow down the dissociation of mazindol from its site and this effect was not sodium-sensitive. These complexities can be accomodated by a model that involves overlapping sites for mazindol and dopamine on the dopamine uptake carrier complex, and translocation -reorientation steps.
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Abbreviations
- K d :
-
dissociation rate constant
- HEPES:
-
N-2hydroxyethyl-piperazine-N′-2-ethanesulfonic acid
- Km:
-
half-saturating concentration for uptake
- B max :
-
maximal binding capacity
- V max :
-
maximal initial uptake rate
- k −1 :
-
dissociation rate constant
- IC50 :
-
concentration of inhibitor causing 50% inhibition
- DA:
-
3,4dihydroxyphenylethylamine (dopamine)
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On leave from the Institute of Experimental Medicine, H-1450, Budapest, P.O.B. 67, Hungary.
Send offprint request to I. Zimányi at her present address
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Zimányi, I., Lajtha, A. & Reith, M.E.A. Comparison of characteristics of dopamine uptake and mazindol binding in mouse striatum. Naunyn-Schmiedeberg's Arch. Pharmacol. 340, 626–632 (1989). https://doi.org/10.1007/BF00717737
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DOI: https://doi.org/10.1007/BF00717737