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Biochemical and Pharmacological Characterization of $[^{3}$H]GBR 12935 Binding In Vitro to Rat Striatal Membranes: Labeling of the Dopamine Uptake Complex
| Content Provider | Scilit |
|---|---|
| Author | Andersen, Peter H. |
| Copyright Year | 1987 |
| Description | Journal: Journal of Neurochemistry Binding of the selective dopamine (DA) uptake inhibitor $[^{3}$H]GBR 12935 to rat striatal membranes was characterized biochemically and pharmacologically. $[^{3}$H]-GBR 12935 binding at 0°C was reversible and saturable and Scatchard analysis indicated a single binding site with a $K_{D}$ of 5.5 nM and a $B_{max}$ of 760 pmol/mg tissue. $[^{3}$H]GBR 12935 labeled two binding sites. One binding site was identified as the classic DA uptake site, since methylphenidate, cocaine, diclofensine, and Lu 19–005 potently inhibited $[^{3}$H]GBR 12935 binding to it. Binding to the second site was inhibited by high concentrations of the above compounds. $IC_{50}$ values for inhibition of $[^{3}$H]GBR 12935 binding to the DA uptake site were proportional to IC50 values for inhibition of DA uptake. However, substrates of DA uptake, e.g., DA and 1-methyl-4-phenylpyridine, and DA releasers, e.g., the amphetamines, inhibited $[^{3}$H]GBR 12935 binding less than DA uptake. Rate experiments excluded the possibility that these “weak” inhibitors affected the binding by alloste-ric coupled binding sites. The second binding site was not a noradrenergic, serotonergic, or GABAergic uptake site. Neither was it a dopaminergic, acetylcholinergic, histaminic, serotonergic, or adrenergic receptor. However, $[^{3}$H]GBR 12935 was potently displaced from it by disubstituted piper-azine derivatives, i.e., flupentixol and piflutixol. DA uptake and the DA uptake binding site of $[^{3}$H]GBR 12935 were located primarily in the striatum, but the piperazine acceptor site was distributed uniformly throughout the brain. Also only the DA uptake binding site was destroyed by 6-OH-DA. Thus, $[^{3}$H]GBR 12935 labels the classic DA uptake site in rat striatum and also a piperazine acceptor site. Substrates for DA uptake and releasers of DA inhibited $[^{3}$H]GBR 12935 binding with low potency, but did not alter the rate constants for $[^{3}$H]GBR 12935 binding. Therefore inhibitors of DA uptake label the carrier site and prevent the carrier process. |
| Related Links | https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1471-4159.1987.tb05752.x |
| Ending Page | 1896 |
| Page Count | 10 |
| Starting Page | 1887 |
| e-ISSN | 14714159 |
| DOI | 10.1111/j.1471-4159.1987.tb05752.x |
| Journal | Journal of Neurochemistry |
| Issue Number | 6 |
| Volume Number | 48 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 1987-06-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Neurochemistry [3h]gbr 12935 Binding 1-methyl-4-phenylpyridine (mpp+) |
| Content Type | Text |
| Resource Type | Article |
