シグマ受容体リガンドの薬理作用　　シグマ受容体の機能　　電気生理学的アプローチ

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タイトル別名
  • Pharmacological Effects of .SIGMA.-Receptor Ligands. The function of sigma receptors-Electrophysiological approach.
  • シグマ ジュヨウタイ ノ キノウ デンキ セイリガクテキ アプローチ
  • シグマ受容体リガンドの薬理作用

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The functions of sigma (σ) receptors were reviewed based on electrophysiological studies. Systemic administration of σ ligands reportedly produces a variety of effects on dopamine (DA) neurons. In the mesolimbic DA system, (+)SKF-10, 047 suppressed activities of the ventral tegmental area. In the substantia nigra, DTG also suppressed these activities, while BMY-14802 increased the activity of neurons. In the cerebellum, however, activities of Purkinje cells were suppressed by locally applied DTG, with probable involvement of the catecholaminergic system. This effect on Purkinje cells may explain the action of σ ligands on the motor system. In the hippocampus, neuronal activities were inhibited by SR31742A in vivo (CA3 region) and by (+)SKF10, 047 in vitro (CA1 region). DTG at high concentration (1 mM) completely suppressed population spikes (PS) in the CA1 region of hippocampal slice preparations. In our experiments, a novel σ ligand, OPC-24439, suppressed PS in CA1 at concentrations of 1-100 μM. However, NMDA-induced neuronal firings in CA3 in vivo were augmented by low doses of DTG in a haloperidolsensitive manner, but high doses were ineffective. In contrast, non-NMDA responses were not affected by DTG. In addition, several σ ligands having no effect on the NMDA response have been reported. In addition, endogenous ligands, neuropeptide Y and dehydroepiandrosterone, augmented the NMDA-induced firing. In whole-cell patch clamp recording, NMDA-induced currents were suppressed by a relatively higher concentration of DTG in a concentration-dependent manner, while non-NMDA responses were only slightly suppressed. These findings suggest that effects of σ ligands on NMDA receptor responses are biphasic, and σ ligands may modulate memory and learning and suppress neuronal death by anoxia. In addition, σligands are also reported to suppress Ca2+ channels in hippocampal culture neurons and induce current by closing α2 channels in NCB-20 cells. Thus, σ receptors may be involved in the modulation of a variety of neurons that relate to psychiatric function and plasticity.

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