ABSTRACT
L-amino acid transporter 1 ( LAT1) is a member of L-amino transporter family and an important heterodi?meric amino acid transporter that belongs to subfamily of SLC7. LAT1 mainly mediates trans-membrane transportation of those neutral amino acids that had cyclobenzene or long side chains with high molecular mass such as L-Leu, L-Met and L-Phe as well as some amino acid analogues such as melphalan, L-DOPA and thyroxine in a Na+and ATP-independent diffu?sion. As LAT1 was abnormally overexpressed in various transformed cell lines, it might be related with tumor stage and prog?nosis. It is not only a biomarker that specifically expressed in some tumor cells but also plays an important role in tumor diag?nosis and therapy. Here we demonstrate the structure of LAT1 and its mechanism in transport peculiarity. We also reviewed the development of LAT1 in tumor diagnosis and treatment.
ABSTRACT
Objective To investigate the changes in the expression of glutamate-aspartste transporter in spinal dorsal horn in rats with inflammatory pain and chronic morphine tolerance. Methods Thirty healthy male SD rats in which intrathecal (IT) catheters were successfully placed without complications were randomized into 3 groups ( n = 10 each): normal saline group ( group NS), arthritis group ( group A), and arthritis + morphine group (group AM). NS 50 μl was injected into the ankle joint of the left hindlimb in group NS, while complete Freund's adjuvant was injected in the other two groups instead. After 3 days, group NS and A received IT NS 10 μl twice a day for 7 consecutive days, group AM IT morphine 10 μg (10 μl) twice a day for 7 consecutive days. Mechanical pain threshold (MPT) was measured before IT administration and at day 2, 4, 6 and 8 after IT administration (T0-4). The animals were sacrificed after the last MPT measurement. The spinal cords were isolated for determination of GLAST expression in spinal dorsal horn. Results Compared with group NS, MPT was significantly decreased in the other groups and GLAST expression was down-regulated in group AM (P ＜ 0.05). Compared with group A, no significant change was found in MPT at T3,4 (P ＞ 0.05), while GLAST expression was down-regulated in group AM ( P ＜ 0.05). Conclusion The development of chronic morphine tolerance is related to the decrease in the function of GLAST in spinal dorsal horn in rats with inflammatory pain.
ABSTRACT
Objective To investigate the effect of intrathecal γ-aminobutyric acid transporter-1 ( GAT-1 )small interfering RNA (siRNA) on neuropathic pain in rats. Methods Male SD rats weighing 200-250 g were studied. The experiment was performed in 3 parts. Part Ⅰ Twenty rats were randomly divided into 5 groups ( n =4 each): GAT-1 siRNA-1 group, GAT-1 siRNA-2 group, GAT-1 siRNA-3 group, negative control siRNA group and DEPC treatment group. Two days after ligation of sciatic nerve, intrathecal siRNA 2 μg or equal volume of DF-PC was injected once a day for 3 consecutive days. The rats were killed and the lumbar segment of the spinal cord was removed at 2nd day after the last intrathecal injection for determination of the expression of GAT-1 in the spinal dorsal horn by Western Blot. Part Ⅱ Thirty rats were randomly divided into 3 groups ( n = 10 each): GAT-1 siRNA-3 + lipo2000 group, GAT-1 siRNA-3 mismatch siRNA + lipo2000 group, and DEPC treatment + lipo2000group. Paw-withdrawl threshold (PWT) to thermal and mechanical stimulation was measured before ligation of sciatic nerve, 3 days after ligation of sciatic nerve and at 1, 3, 5, 7 and 10 days after consecutive administration for 3 days. Part Ⅲ Eighty-four rats were randomly divided into 3 groups as described in Part Ⅱ ( n = 28 each). Four rats were killed at each time point and the lumbar segment of the spinal cord was removed for determination of the expression of GAT-1 in the spinal dorsal horn by Western blot. Results PWT to thermal and mechanical stimulation was significantly inreased and the GAT-1 expression was down-regulated after the injection of GAT-1 siRNA.Conclusion Intrathecal GAT-1 siRNA can reduce the neuropathic pain by inhibiton of up-regulation of the GAT-1 expression in the spinal dorsal horn in rats.