Abstract:
:The kinetics of the association and dissociation of the tritium-labeled selective and potent dopamine transporter inhibitor N-(3-iodoprop-2E-enyl)-2beta-carbo-[3H]methoxy-3beta-(4'-methylphenyl)nortropane ([3H]PE2I) with the transporter of mouse striatal membranes was studied. The analysis revealed that the specific binding of [3H]PE2I occurs within a homogeneous population of binding sites in these membranes. The relatively slow binding process was characterized by the pseudo-first-order rate constant kobs. The plot of these rate constants versus free radioligand concentration was hyperbolic, demonstrating that at least two kinetically distinguishable steps can be identified in the interaction of dopamine transporter with this inhibitor. The fast and reversible binding step, characterized by dissociation constant KA = 51 +/- 23 nM, is followed by a slow but also reversible isomerization step of the complex, characterized by the isomerization rate constant ki = (7 +/- 2)10(-2) s(-1) and by the rate constant k(-i) = (3.9 +/- 0.5)10(-3) s(-1) for the reverse process. This isomerization step increases the apparent affinity of the ligand and probably consists of a conformational transition of the transporter protein, induced by the inhibitor molecule.
journal_name
Neurosci Lettjournal_title
Neuroscience lettersauthors
Stepanov V,Järv Jdoi
10.1016/j.neulet.2006.10.007subject
Has Abstractpub_date
2006-12-27 00:00:00pages
218-21issue
3eissn
0304-3940issn
1872-7972pii
S0304-3940(06)01057-3journal_volume
410pub_type
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