Pasternak Gavril W
Department of Neurology and Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10021, USA.
Department of Neurology, Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.
Handb Exp Pharmacol. 2017;244:163-175. doi: 10.1007/164_2017_34.
Since their proposal in 1976, the concept of sigma receptors has been continually evolving. Initially thought to be a member of the opioid receptor family, molecular studies have now identified its genes and established its structure crystallographically. Much effort has now revealed its importance as a chaperone in the endoplasmic reticulum, but its functions extend beyond this. Sigma receptors have been associated with a host of signaling systems. Evidence over the past 20 years has established the modulatory effects of sigma ligands on opioid systems. Despite their inability to bind directly to opioid receptors, sigma ligands can modulate opioid analgesia in vivo and signal transduction mechanisms in vitro. Furthermore, sigma receptors can physically associate with GPCRs. Together, these findings show that sigma ligands can function as allosteric modulators of GPCR function through their association with the sigma receptors, which are in direct physical association with opioid receptors, members of the G-protein coupled family of receptors.
自1976年提出以来，σ受体的概念一直在不断演变。最初被认为是阿片受体家族的一员，现在分子研究已经确定了它的基因，并通过晶体学确定了其结构。现在许多研究工作已经揭示了它作为内质网伴侣的重要性，但其功能不止于此。σ受体与许多信号系统有关。过去20年的证据证实了σ配体对阿片系统的调节作用。尽管它们不能直接与阿片受体结合，但σ配体可以在体内调节阿片类镇痛作用，并在体外调节信号转导机制。此外，σ受体可以与G蛋白偶联受体（GPCRs）发生物理结合。这些发现共同表明，σ配体可以通过与σ受体结合，作为GPCR功能的变构调节剂，而σ受体与阿片受体直接发生物理结合，阿片受体是G蛋白偶联受体家族的成员。
