Peptide displacement of [3H]5-hydroxytryptamine binding to bovine cortical membranes.
Chemical studies have demonstrated that peptides such as the encephalitogenic (EAE) peptide of myelin basic protein (MBP) and luteinizing hormone-releasing hormone (LHRH) can bind serotonin (5-hydroxytryptamine, 5-HT) in vitro. The present research was undertaken to determine whether such binding interferes with 5-HT binding to its 5-HT1 receptors on bovine cerebral cortical membranes. EAE peptide and LHRH displaced [3H]5-HT with IC50s of 4.0 x 10(-4) and 1.8 x 10(-3) M respectively. MBP itself also showed apparent displacing ability with an IC50 of 6.0 x 10(-5) M, though it also caused aggregation of cortical membranes that might have interfered with normal receptor binding. These results support previous suggestions that the tryptophan peptide region of MBP may act as a 5-HT receptor in the neural system. We also tested the effects of muramyl dipeptide (N-acetyl-muramyl-L-Ala-D-isoGln, MD), a bacterial cell-wall breakdown product that acts as a slow-wave sleep promoter, binds to LHRH and EAE peptide, and competes for 5-HT binding sites on macrophages. It showed no significant displacement of 5-HT binding to cortical membranes (IC50 greater than 10(-1) M), but its D-Ala analogue did (IC50 = 1.7 x 10(-3) M). Thus, it seems likely that the 5-HT-related effects of naturally occurring muramyl peptides are physiologically limited by receptor types.
Takeuchi
Y
Y
Samuel Roberts Noble Foundation, Inc., Biomedical Division, Ardmore, OK 73402.
Root-Bernstein
R S
RS
Shih
J C
JC
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002540:Cerebral Cortex / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D008566:Membranes / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D014316:Tritium
D004676:Myelin Basic Protein; D014316:Tritium; D012701:Serotonin; D007987:Gonadotropin-Releasing Hormone; D000119:Acetylmuramyl-Alanyl-Isoglutamine