Serotonin binding sites. II. Muramyl dipeptide binds to serotonin binding sites on myelin basic protein, LHRH, and...

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.