Interleukin-2 modulates N-methyl-D-aspartate receptors of native mesolimbic neurons.
Interleukin-2 modulates N-methyl-D-aspartate receptors of native mesolimbic neurons.
复制标题
Interleukin-2 调节天然中边缘神经元的 N-甲基-D-天冬氨酸受体。
DOI：
10.1016/s0006-8993(01)02056-x
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发表时间：
2001
期刊：
影响因子：
2.9
通讯作者：
Zalcman,SS
中科院分区：
文献类型：
--
作者：
Ye,JH;Tao,L;Zalcman,SS
Interleukin (IL)-2 is a brain-derived cytokine that influences mesocorticolimbic dopamine release, and is associated with pathological outcomes that are mediated, at least in part, by aberrations in mesolimbic neurotransmission. The mechanisms by which IL-2 modulates mesolimbic transmission, however, are not known. The NMDA receptor/channel (NMDAR) plays an essential role in neuronal excitability of mesolimbic neurons; we thus examined in neonatal rats the effects of IL-2 on NMDA-activated current (INMDA) in voltage-clamped neurons freshly isolated from the ventral tegmental area (VTA), the site of origin of the mesolimbic system. IL-2 (0.01–500 ng/ml) alone had no effect on membrane conductance. When co-applied with NMDA, IL-2 (50–500 ng/ml) significantly potentiated INMDA. In contrast, doses as low as 0.01 ng/ml markedly decreased the NMDA response. Dose–response analysis showed that IL-2 (>50 ng/ml) increased the maximal INMDA, without changing the EC50, indicating that IL-2 potentiates INMDAby increasing the efficacy of the NMDAR. Moreover, current–voltage analysis revealed that IL-2 potentiation of INMDAwas voltage-dependent, being greater at negative potentials. In contrast, IL-2 inhibition of INMDAwas voltage-independent, and IL-2 did not alter the reversal potential. Additionally, IL-2 (1 ng/ml) shifted the NMDA concentration–response curve to the right, significantly increasing the EC50for NMDA without changing the maximal INMDA, suggesting that IL-2 inhibits the NMDAR by a competitive mechanism. IL-2 thus acts as a potent modulator of the NMDAR. IL-2-induced alterations of responses to NMDAR activation may contribute to synaptic plasticity in the mesolimbic system and to pathological outcomes associated with this system.
