Characterization of the release and metabolism of delta sleep-inducing peptide (DSIP) in the rat brain.

In the present study, we examined whether delta sleep-inducing peptide (DSIP) was (1) secreted from neurons on depolarization and (2) degraded by membrane-associated peptidases. Incubation of DSIP with rat brain membrane resulted in the degradation of DSIP with liberation of tryptophan, an N-terminal amino acid of DSIP. Bestatin and puromycin, aminopeptidase inhibitors, significantly inhibited the degradation of DSIP and release of tryptophan. The releases of immunoreactive DSIP-like substance (irDSIP) from rat brain slices and synaptosomes were significantly stimulated by high K(+)-evoked depolarization. The released irDSIP was coeluted with native DSIP on gel filtration chromatography. High K(+)-evoked release of irDSIP did not show extracellular Ca(2+)-dependency. This Ca(2+)-independency suggests that the secretory pathway of DSIP may be different from that of other neurotransmitters. These results demonstrate that DSIP is released from nerve endings on depolarization and inactivated by membrane-associated puromycin-sensitive aminopeptidase. Therefore, DSIP may serve as a neuropeptide-like material in the central nervous systems.