Peptide [D-Ala~]DSIP markedly increases the representation of NREM and REM sleep delayed by several hours from the onset of infusion and lasting after the infusion till the end of the 12-hour night period in a chamber. Peptide [D-TyrqDSIP increases NREM sleep during hours IV and XI of recordings. Analogs of these peptides have no noticeable effects.
Key Words: DSIP peptide; sleep; ratsPeptide DSIP (Delta Sleep-Inducing Peptide) was isolated from rabbit venous cerebral blood by a group of Swiss scientists in 1977. Intensive investigation of this substance undertaken later by different research teams revealed that DSIP or some other peptide(s) similar in structure is present, free or bound, in the peripheral organs, tissues, and fluids of the body, as well as in the pituitary, hypothalamus, and limbic system of the brain, where it is localized together with a number of peptide and nonpeptide transmitters [2,6,8,14]. There are data on the participation of this peptide in quite a number of normal and abnormal reactions (stress, immune, pain, endocrine), as well as in the regulation of the circadian rhythms, the formation of alcohol and opioid dependence, etc. [2,6,9]. Paradoxically, the "primary" function of this substance -sornniferous -is doubted by many workers, and a number of experiments on rabbits and rats, including our own, have not confn'med it [2,5]. However, later we demonstrated that ff the N- terminal tryptophan residue were replaced by its Disomer or tyrosine D-isomer or ff the alanine residue in the second position were replaced by its D-isomer in the DSIP molecule (such alterations greatly improve molecular resistance to the destructive action of aminopeptidases), the analogs developed a capacity to prolong NREM and REM sleep in rabbits and rats for intraventricular injection [2][3][4]. This agrees with the results of in vivo and in vitro biochemical studies which showed that a DSIP molecule introduced from the outside rapidly disintegrated under the effect of specific amino peptidase and its halflife in the body was just a few minutes [2,6,9]. After the splitting off of the tryptophan N-terminal residue, the horseshoe coiled conformation assumed by the DSIP molecule in aqueous solutions breaks down, this leading to inactivation of the peptide [12].We studied the effects on rat sleep of 4 DSIP analogs characterized by increased resistance to ami-
MATERIALS AND METHODSAdult male inbred rats with preimplanted (under barbituric narcosis, 45 rng/kg intraperitoneally) ele-000%4888/94/0001-0058512.50 9Plenum Publishing Corporation