ISSN:
1432-1912
Keywords:
Key words Dopamine transporter
;
WIN 35
;
428 binding
;
N-ethylmaleimide
;
Sulfhydryl groups
;
Rat striatum
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Binding sites for 2β-carbomethoxy-3β-(4-fluorophenyl)[3H]tropane ([3H]WIN 35,428) on rat striatal membranes were alkylated with N-ethylmaleimide (NEM), and the protective potency was measured of the blockers cocaine, N[1-(2-benzo[b]thiophenyl) cyclohexyl]piperidine (BTCP), benztropine, WIN 35,428, and nomifensine, and of the substrates dopamine, norepinephrine, S(+)-amphetamine, tyramine, and metaraminol. In general, the protective potency was lower (at least 3 times) than the potency in inhibiting [3H]WIN 35,428 binding with the compounds present under the same experimental conditions used for the NEM-induced alkylation. However, the disparity was substantially greater for all substrates tested (10- to 93-fold) than for the blockers (2- to 6-fold), especially cocaine and BTCP (3-fold). [3H]WIN 35,428 binding was best described by a 1-site model under the present conditions. The results are discussed in terms of models involving blocker-induced conformational changes and overlapping nonidentical binding domains for blockers and substrates.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/PL00004919
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