Reverse structure of carnosine-induced sedative and hypnotic effects in the chick under acute stress

In the central nervous system, β-alanine is thought to act as an inhibitory neurotransmitter, but the role or precise mechanism of β-alanine in the brain has not been clearly defined. β-Alanine is found in high levels in the chicken brain as a component of the dipeptides carnosine (β-alanyl-l-histidine) and anserine, or as a free amino acid. We focused on the position of β-alanine, i.e., at the carboxyl terminus. In Experiment 1, the central effects of glycyl-β-alanine, l-histidyl-β-alanine and l-valyl-β-alanine were compared with a saline control in chicks. l-Histidyl-β-alanine significantly induced sedative and hypnotic effects. In Experiment 2, the effects of carnosine, its reverse (l-histidyl-β-alanine), and their combination were investigated. Central carnosine-induced hyperactivity while reverse carnosine-induced hypoactivity, and the behaviors were intermediate following the combination of the two peptides. Finally, the central effect of reverse carnosine was compared with β-alanine alone and l-seryl-β-alanine in Experiment 3. Reverse carnosine showed similar effects to β-alanine. In conclusion, l-histidyl-β-alanine not only has the reverse structure of carnosine, but also reverse function. Thus, we propose to name reverse carnosine (l-histidyl-β-alanine) rev-carnosine.