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• W1976572191 abstract "The biochemical and pharmacological characteristics of sodium-dependent [3H]GBR12935 ([3H]GBR) binding to homogenates of rat, mouse, guinea-pig and dog striatum were determined at 23°C. In mouse striatum, [3H]GBR binding was also compared with [3H]dopamine ([3H]DA) uptake. Specific [3H]GBR binding to the dopamine (DA) transport complex (DTC) represented ⩾ 70% of the total binding and was saturable, reversible and involved a single class of non-interacting sites in the rodent and dog striatal homogenates. The dog DTC exhibited a significantly higher affinity (mean ± SEM) (Kd = 1.8 ± 0.6 nM, P < 0.02-0.01) than the guinea-pig and a lower binding capacity (Bmax = 0.6 ± 0.1 pmol/mg protein; P < 0.05-0.01) than the rat (Kd = 2.3 ± 0.2 nM; Bmax = 2.1 ± 0.17 pmol/mg) and guinea-pig (Kd = 4.9 ± 0.49 nM; Bmax = 1.9 ± 0.35 pmol/mg) (n = 3–4) striatum. [3H]GBR binding to the striatal DTC in the rodents and dog was competitively inhibited by unlabelled GBR 12909 (Ki = 6–12 nM), mazindol (Ki = 106–216 nM), benzotropin (Ki = 113–335 nM), nomifensine (Ki = 0.7–2.6 μM), cocaine (Ki = 1–2.3 μM), phencyclidine (Ki = 1.6–2.6 μM) and amfonelic acid (1–6 μM). Compounds with Ki ⩾ 6–10 μM included dopamine, d,l-amphetamine and spiperone. In general, the majority of the compounds appeared to be more active competitors of [3H]GBR binding in the dog striatum as compared to the rodent tissues, but the rank order of activity was identical in the dog and all the rodents. Numerous other compounds, such as desipramine, norepinephrine, epinephrine, amitriptyline, propranolol, histamine, etc. were essentially inactive at 1 μM against [3H]GBR binding. [3H]DA uptake into mouse striatal synaptosomes was competitively inhibited by amfonelic acid (IC50 = 25 nM), GBR12909 (IC50 = 35 nM), DA (IC50 = 106 nM), benzotropin (IC50 = 175 nM), mazindol (IC50 = 252 nM), cocaine (IC50 = 0.8 μM) and phencyclidine (IC50 = 1.2 μM). Apart from amfonelic acid and DA, there was a good correlation (R = 0.88) between the relative potency of the above compounds at inhibiting [3H]DA uptake and competing for [3H]GBR binding in the mouse striatum. These studies have therefore shown that the biochemical and pharmacological properties of [3H]GBR binding to the rodent and dog DTC are similar, and that [3H]GBR is a good marker for the [3H]DA uptake inhibitor site." @default.
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• W1976572191 date "2007-03-01" @default.
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• W1976572191 title "P.1.36 Identification and validation of new antidepressant-responsive gene candidates in mouse brain" @default.
• W1976572191 doi "https://doi.org/10.1016/s0924-977x(07)70037-8" @default.
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