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Notes: Abstract  1-Methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is efficiently taken up and accumulated by rat hepatocytes. However, the nature of the mechanism(s) involved in the hepatic uptake of MPP+ remains partially unknown. The aim of the present study was to further characterize the hepatic uptake of 3H-MPP+, namely by investigating the interactions of catecholamines (which are also efficiently taken up by rat hepatocytes) with MPP+ transport. The accumulation of 3H-MPP+ in isolated rat hepatocytes occurred through saturable and non-saturable mechanisms. The kinetics of the saturable component of 3H-MPP+ uptake was as follows: Vmax= 181.3±11.1 pmol mg protein-1 min-1 and Km= 47.1 μM (27.9, 66.3) (n=5). The diffusion constant (in ml mg protein-1 min-1) for the non-saturable uptake of 3H-MPP+ was 0.00068 (0.00052, 0.00083) (n=5). From the analysis of the time course of 3H-MPP+ accumulation at a substrate concentration of 100 nM 3H-MPP+, it was found that the rate constant of inward transport of 3H-MPP+ into hepatocytes (kin) was 15.7±3.8 μl mg protein-1 min-1, the rate constant of outward transport of 3H-MPP+ from hepatocytes (kout) was 0.077± 0.023 min-1 and the equilibrium accumulation (Amax) of 3H-MPP+ was 20.2±2.0 pmol mg protein-1 (n=36). Decynium22 (1,1′-diethyl-2,2′-cyanide; 1 μM) significantly reduced kin to 6.1±1.8 μl mg protein-1 min-1 (P〈0.05) and the equilibrium accumulation (Amax) of 3H-MPP+ to 9.6±1.3 pmol mg protein-1 (P〈0.005) (n=36). 3H-MPP+ accumulation (in cells incubated with 200 nM 3H-MPP+) was sensitive to (−)-adrenaline, (−)-isoprenaline, (−)-dopamine, (±)-adrenaline and (−)-noradrenaline. The most potent catecholamine in inhibiting 3H-MPP+ uptake was (−)-adrenaline, with an IC50 of 99 (22, 449) μM (n=6). (−)-Adrenaline competitively inhibited 3H-MPP+ uptake, as it significantly increased the Km value of 3H-MPP+ uptake (to 125.4 μM (63.6; 187.1); P〈0.02; n=3) but did not change the Vmax value. The cyanine-derivatives decynium22 and cyanine863 (1-ethyl-2-([1,4-dimethyl-2-phenyl-6-pyrimidinylidene] methyl)quinolinium), which inhibit uptake2 as well as the apical type of the renal transporter for organic cations, potently inhibited 3H-MPP+ uptake with IC50’s of 1.4 (0.4–5.3) (n=6) and 6.5 (2.6–16) (n=4) μM, respectively. Under conditions of monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) inhibition (with either pargyline (500 μM)+Ro01-2812 (3,5-dinitropyrocatechol; 2 μM) or pargyline (500 μM) +U-0521 (3,4-dihidroxy-2-methyl-propiophenone; 12 μM)), (−)-adrenaline (up to 1 mM) had no inhibitory effect on the uptake of 3H-MPP+. Moreover, the uptake of 3H-MPP+ in the presence of pargyline+Ro 01-2812 was significantly lower (66.9±30.4%; P〈0.05; n=4) than in the absence of these compounds. Therefore, the effect of these MAO and COMT inhibitors on 3H-MPP+ uptake was examined. Interestingly enough, pargyline, Ro 01-2812 and U-0521 were found to inhibit the uptake of 3H-MPP+ (in cells incubated with 200 nM 3H-MPP+): 500 μM pargyline, 2 μM Ro 01-2812 and 100 μM U-0521 decreased the accumulation of 3H-MPP+ to 38.1±6.8 (n=5), 60.5±10.1(n=7) and 71.3±14.5 (n=7) % of control, respectively. It is concluded that 3H-MPP+ is efficiently taken up by rat hepatocytes by a carrier-mediated mechanism sensitive to catecholamines, decynium22 and cyanine863, and to the enzyme inhibitors pargyline, Ro 01-2812 and U-0521.

Notes: Abstract We solve exactly the problem of a one-dimensional repulsive-U Hubbard chain with toroidal boundary conditions (HTB) using the Bethe ansatz approach. We calculate analytically the finite-size corrections to the ground-state energy in the half-filled case and use this expression to derive charge and spin stiffnesses with no assumptions. We then use a “particle-hole” transformation to calculate the finite-size corrections for the half-filledattractive- U case, and again derive the resulting expressions for the charge and spin stiffnesses. Lastly, we discuss how the repulsive-U corrections relate to those of a Heisenberg model with toroidal boundary conditions.