Root-Bernstein R S, Westall F C
Department of Physiology, Michigan State University, East Lansing 48824.
Brain Res Bull. 1990 Dec;25(6):827-41. doi: 10.1016/0361-9230(90)90178-3.
Previously, we reported the existence of structurally similar serotonin binding sites on myelin basic protein, LHRH, and MSH-ACTH 4-10. We now report that the adjuvant peptide, muramyl dipeptide (N-acetyl-muramyl-L-Ala-D-isoGln) also binds to these sites. This observation may help to explain previous observations of serotonin-like activity by muramyl peptides, including the promotion of slow-wave sleep and fever induction. The observation may also provide an important link between the immune system and the nervous system that may explain the role of muramyl dipeptide adjuvants in causing autoimmune diseases to serotonin-regulated proteins and their receptors, as well as the alterations in serotonin levels that are often observed in autoimmune diseases. The observation provides concrete evidence for a dual-antigen hypothesis for the induction of autoimmune diseases by an adjuvant-peptide complex. Application of such a mechanism for induction of autoimmunity may be of importance in understanding a number of postinfectious and postvaccinal neuropathies, and suggests a possible etiology for autism, in which many patients have high blood serotonin levels, autoimmune reactions to myelin basic protein, and antibodies to serotonin binding sites. Finally, the observation suggests that glycopeptides may act as neurotransmitters.
此前，我们报道了在髓鞘碱性蛋白、促黄体生成素释放激素（LHRH）和促黑素-促肾上腺皮质激素4-10上存在结构相似的5-羟色胺结合位点。我们现在报道辅助肽胞壁酰二肽（N-乙酰胞壁酰-L-丙氨酸-D-异谷氨酰胺）也能结合这些位点。这一观察结果可能有助于解释此前关于胞壁酰肽具有5-羟色胺样活性的观察结果，包括对慢波睡眠的促进作用和发热诱导作用。该观察结果还可能在免疫系统和神经系统之间提供一个重要联系，这或许可以解释胞壁酰二肽佐剂在引发针对5-羟色胺调节蛋白及其受体的自身免疫性疾病中的作用，以及自身免疫性疾病中经常观察到的5-羟色胺水平变化。这一观察结果为佐剂-肽复合物诱导自身免疫性疾病的双抗原假说提供了具体证据。应用这种自身免疫诱导机制可能对于理解许多感染后和疫苗接种后神经病变具有重要意义，并提示了自闭症的一种可能病因，在自闭症中许多患者血液中5-羟色胺水平较高、对髓鞘碱性蛋白有自身免疫反应以及存在针对5-羟色胺结合位点的抗体。最后，该观察结果表明糖肽可能作为神经递质发挥作用。
