Tidjane Corera A, Do-Régo J C, Costentin J, Bonnet J J
UMR C.N.R.S. 6036, IFRMP 23, U.F.R. de Médecine et Pharmacie, 22 Boulevard Gambetta, 76000, Rouen, France.
Neurosci Res. 2001 Mar;39(3):319-25. doi: 10.1016/s0168-0102(00)00230-3.
Addition of NaCl (90--290 mM) to a 10 mM Na(+) medium did not significantly modify B(max) and K(d) values for [3H]mazindol binding to the dopamine neuronal transporter (DAT) studied on rat striatal membranes at 20 degrees C. Addition of NaCl differentially affected the ability of other uptake inhibitors and substrates to block the [3H]mazindol binding. Ratios of 50% inhibiting concentrations calculated for 290 and 90 mM NaCl allowed to distinguish three groups of agents: substrates which were more potent in the presence of 290 mM NaCl (group 1; ratio < 1) and two groups of uptake inhibitors displaying ratio values either ranging around two (group 2: WIN 35,428, cocaine, methylphenidate, pyrovalerone) or close to unity (group 3: BTCP, mazindol, benztropine, nomifensine). However, agents from these three groups recognize mutually exclusive binding sites since in interaction studies the presence of WIN 35,428 (group 2) or mazindol (group 3) increased the 50% inhibiting concentrations of D-amphetamine (group 1) and WIN 35,428 on the [3H]mazindol binding to theoretical values expected for a competition of all of these compounds for the same binding domain on the DAT.
在20℃下，向10 mM Na⁺ 培养基中添加NaCl（90 - 290 mM），对[³H]麦角乙脲与大鼠纹状体膜上多巴胺神经元转运体（DAT）结合的B(max)和K(d)值没有显著影响。添加NaCl对其他摄取抑制剂和底物阻断[³H]麦角乙脲结合的能力有不同影响。计算290 mM和90 mM NaCl条件下50%抑制浓度的比值，可以区分出三组试剂：在290 mM NaCl存在时更有效的底物（第1组；比值<1），以及两组摄取抑制剂，其比值分别约为2（第2组：WIN 35,428、可卡因、哌醋甲酯、吡咯戊酮）或接近1（第3组：BTCP、麦角乙脲、苯海索、诺米芬辛）。然而，这三组试剂识别相互排斥的结合位点，因为在相互作用研究中，WIN 35,428（第2组）或麦角乙脲（第3组）的存在会使D-苯丙胺（第1组）和WIN 35,428对[³H]麦角乙脲结合的50%抑制浓度增加到理论值，该理论值是所有这些化合物竞争DAT上相同结合域时所预期的。
