The study shows that the sleep‑inducing peptide DSIP (and a couple of its variants) can move from the bloodstream into the brain fluid of dogs after an IV injection, meaning it does cross the blood‑brain barrier. The peptide sticks to a large protein in the blood, and the free form appears to be what gets into the brain. This suggests DSIP’s effects on sleep and possibly other brain functions are likely due to a real, direct action in the central nervous system.

To determine if the nonapeptide delta sleep-inducing peptide (DSIP) and some of its analogs can enter the cerebrospinal fluid (CSF) from the peripheral circulation, dogs anesthetized with sodium pentobarbital were injected with a 100 micrograms/kg bolus of DSIP, desTrp1-DSIP, or D-Ala3-DSIP. Using an antibody that is highly specific for these nonapeptides, we found significant increases in CSF after IV injection of each. Column chromatography of CSF withdrawn after an IV bolus of DSIP showed the increase in immunoreactivity to be due to DSIP and desTrp1-DSIP. Chromatography of radioactivity appearing in the CSF after an IV bolus of 125I-N-Tyr-DSIP showed co-elution with the intact labeled peptide. The CSF/plasma ratios for DSIP and 125I-N-Tyr-DSIP were higher than that for tritiated insulin injected IV. It was also shown that DSIP is reversibly bound to a large molecule in dog plasma and CSF, and that the binding is greater in blood than in CSF. The binding protein demonstrates some specificity for DSIP, binding a smaller percentage of D-Ala3-DSIP, and it appears that it is probably free DSIP that crosses the blood-brain-barrier. Although non-specific crossing cannot be ruled out, the results presented here are also consistent with a specific saturable process for DSIP.