Delta sleep-inducing peptide, abbreviated DSIP, is a neuropeptide that when infused into the mesodiencephalic ventricle of
recipient rabbits induces spindle and delta EEG activity and reduced motor activities.
Its aminoacid sequence is Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu. However, the gene is unknown, raising serious questions regarding the actual existence of this peptide in nature.
Delta sleep-inducing peptide was first discovered in 1974 by the Swiss Schoenenberger-Monnier group who isolated it from the cerebral venous blood of rabbits in an induced state of sleep. It was primarily believed to be involved in sleep regulation due to its apparent ability to induce slow-wave sleep in rabbits, but studies on the subject have been contradictory.
Delta-sleep-inducing peptide (DSIP)-like material has been found in human breast milk.
Structure and Interactions
DSIP is an amphiphilic peptide of molecular weight 850 daltons with the amino acid motif: N-Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu-C
In the brain its action may be mediated by NMDA receptors. In another study Delta sleep-inducing peptide stimulated Acetyltransferase activity through α1 receptors in rats. It is unknown where DSIP is synthesized.
In vitro it has been found to have a low molecular stability with a half life of only 15 minutes due to the action of a specific aminopeptidase-like enzyme. It has been suggested that in the body it complexes with carrier proteins to prevent degradation, or exists as a component of a large precursor molecule, but as yet no structure or gene has been found for this precursor.
Gimble et al. suggest that DSIP interacts with components of the MAPK cascade and is homologous to glucocorticoid-induced leucine zipper (GILZ). GILZ can be induced by Dexamethasone. It prevents Raf-1 activation, which inhibits phosphorylation and activation of ERK.
Many roles for DSIP have been suggested following research carried out using peptide analogues with a greater molecular stability and through measuring DSIP-like immunological (DSIP-LI) response by injecting DSIP antiserum and antibodies.
There is also conflicting evidence as to its involvement in sleep patterns. Some studies suggest a link between DSIP and slow-wave sleep (SWS) promotion and suppression of paradoxical sleep, (PS) while some studies show no correlation. Stronger effects on sleep have been noted for the synthesized analogues of DSIP.
It may affect human lensepithelial cell function via the MAPK pathway, which is involved in cell proliferation, differentiation, motility, survival, and apoptosis.
Roles in disease and medicine
It has been found to have anticarcinogenic properties. In a study on mice, injecting a preparation of DSIP over the mice's lifetime decreased total spontaneous tumor incidence 2.6-fold.
The same study found it to also have geroprotective effects: it slowed down the age-related switching-off of oestrous function; it decreased by 22.6% the frequency of chromosome aberrations in bone marrow cells and it increased by 24.1% maximum life span in comparison with the control group.
Levels of DSIP may be significant in patients diagnosed with major depressive disorder (MDD). In several studies, levels of DSIP in the plasma and cerebrospinal fluid are significantly deviated from the norm in patients with MDD, though there are contradictions as to whether levels are higher or lower than healthy control patients.
In studies on rats with metaphit-induced epilepsy DSIP acted as an anticonvulsant, significantly decreasing the incidence and duration of fits suggesting DSIP as a potential treatment for epilepsy.
Due to its possible effects on sleep and nociception, trials have been carried out to determine whether DSIP can be used as an anaesthetic. One such study found that administration of DSIP to humans as an adjunct to isoflurane anaesthesia actually increased the heart rate and reduced the depth of anaesthesia instead of deepening it as expected.
In Alzheimer's patients levels of DSIP have been found to be slightly elevated, though this is unlikely to be causal.
A preparation of DSIP, Deltaran, has been used to correct central nervous system function in children after antiblastomic therapy. Ten children aged 3–16 years were given a ten-day course of Deltaran and their bioelectric activity recorded. It was found that the chemotherapy-induced impairment in the bioelectrical activity of 9 out of the 10 children was reduced by administration of DSIP.
DSIP can act antagonistically on opiate receptors to significantly inhibit the development of opioid and alcohol dependence and is currently being used in clinical trials to treat withdrawal syndrome. In one such trial it was reported that in 97% of opiate-dependent and 87% of alcohol-dependent patients the symptoms were alleviated by DSIP administration.
In some studies administration of DSIP has alleviated narcolepsy and normalized disturbed sleeping patterns.
Safety and possible side-effects of long-term DSIP use haven't been established in clinical research studies.
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