Zhang Xu, Bao Lan, Guan Ji-Song
Institute of Neuroscience, Key Laboratory of Neurobiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Trends Pharmacol Sci. 2006 Jun;27(6):324-9. doi: 10.1016/j.tips.2006.04.005. Epub 2006 May 6.
Changes in the number of receptors on the cell surface lead to modulations of physiological functions and pharmacological responses of neurons. Recent studies show that delta-opioid peptide (DOP) and mu-opioid peptide (MOP) receptors have distinct subcellular localizations in neurons. In nociceptive small neurons in the dorsal root ganglia, DOP receptors are sorted into neuropeptide-containing secretory vesicles, enabling the stimulus-induced cell surface expression of these receptors. MOP receptors are constitutively expressed on the cell surface. The physical interaction between DOP receptors and MOP receptors seems to be an important mechanism for the modulation of receptor functions. Experiments in animals show that MOP-receptor-mediated spinal analgesia is enhanced and morphine tolerance does not develop when DOP receptor functions are pharmacologically or genetically attenuated. Thus, the delivery and trafficking of DOP receptors are crucial processes that modulate opioid analgesia and tolerance.
细胞表面受体数量的变化会导致神经元生理功能和药理反应的调节。最近的研究表明，δ-阿片肽（DOP）受体和μ-阿片肽（MOP）受体在神经元中具有不同的亚细胞定位。在背根神经节的伤害性小神经元中，DOP受体被分选到含有神经肽的分泌小泡中，使得这些受体能够在刺激诱导下在细胞表面表达。MOP受体在细胞表面组成性表达。DOP受体与MOP受体之间的物理相互作用似乎是调节受体功能的重要机制。动物实验表明，当DOP受体功能通过药理学或遗传学方法减弱时，MOP受体介导的脊髓镇痛作用增强，且不会产生吗啡耐受性。因此，DOP受体的转运和运输是调节阿片类镇痛和耐受性的关键过程。
