Carnosine release from olfactory bulb synaptosomes is calcium-dependent and depolarization-stimulated.

The dipeptide carnosine (beta-alanyl-L-histidine) has been proposed as a neurotransmitter in the mammalian olfactory pathway. Therefore, the efflux of in vivo-synthesized [14C]carnosine from mouse olfactory bulb synaptosomes was investigated. Carnosine was found to be released from the olfactory bulb synaptosomes by two mechanisms. The first is a slow spontaneous process that is independent of depolarization. The rate of this release was doubled in the presence of 1 mM external carnosine. Release by the second mechanism was markedly stimulated in the presence of calcium by depolarization with either 60 mM K+ or 300 microM veratridine. Omission of calcium abolished the stimulatory effect of both of these agents. Further, blockage of the veratridine-induced depolarization by tetrodotoxin also inhibited carnosine release. These results are consistent with the hypothesis that carnosine acts as a neurotransmitter in the mouse olfactory pathway.