Phospho DSIP: Delta sleep-inducing peptide.
Delta sleep-inducing peptide was first isolated in Switzerland in 1977 from the cerebral-venous blood of sleeping rabbits; since then it has been studied extensively but the primary role of the peptide in mammals is thus far inconclusive as studies have provided many contradictory results. Since the initial paper by Schoenenberger, et al, hundreds of studies have focused on potential primary and peripheral roles of the neuropeptide.
Immunoreactive DSIP has been isolated in the hypothalamus, pituitary, and adrenal glands, which together make up the system known as the HPA axis. Decreased cerebrospinal fluid (CSF) levels and plasma levels are implicated in or associated with major depressive disorder, and reduced CSF levels with schizophrenic states. DSIP has been shown to induce sleep. It has also been used successfully to treat opiate and alcohol withdrawal. It has been shown to work as an analgesic in treatment of chronic pain, sometimes as an adjunct treatment. The source of production of DSIP is unknown; it may be produced in the central nervous system or in a peripheral organ. It is thought to pass through the blood-brain barrier (BBB) more easily than most known neuropeptides.
The amino acid structure of Phospho DSIP is as follows:
H-Trp-Ala-Gly-GlyAsp-Ala-Ser(PO3H2)-GlyGlu-OH. There is an apparent disparity between circulating life in vivo and a lower stability (15 minutes approximately) demonstrated in vitro. This has led to speculation that a carrier protein interacts with endogenous DSIP to enhance stability, or that it is distributed in the form of a larger precursor model, but there is no supporting evidence for these hypotheses at time of writing.
DSIP has been shown to block ACTH release and decrease levels of ACTH, stimulate LH release, and act as an inhibitor of the secretion of somatostatin.
DSIP may have potential as an epileptic treatment; in rats with metaphit-induced epilepsy, it was demonstrated to act as an anti-convulsant.
DSIP has been demonstrated not only to act as an effective treatment for opiate withdrawal, it actually acts as an opiate receptor antagonist, helping prevent formation of opiate dependence.
DSIP has also been shown to help treat narcolepsy and restore disturbed sleep patterns to normal sleep rhythms.
Phospho-DSIP, also known as phosphorylated delta sleep inducing peptide, occurs naturally in the body and is thought to have the same effects (except "stronger" and "more consistent") as DSIP except with a longer circulating life:
125I-N-Tyr-P-DSIP, a phosphorylated analog, revealed slower degradation and, in contrast to DSIP, produced complex formation. An excess of unlabeled material did not displace the radioactivity supporting the assumption of non-specific binding/aggregation. It was concluded that the rapid disappearance of injected DSIP in blood was due to degradation, whereas complex formation together with slower degradation resulted in longer persistence of apparently intact analogs. Whether this could explain the sometimes stronger and more consistent effects of DSIP-analogs remains to be examined.
Schoenenberger GA, Maier PF, Tobler HJ and Monnier M. A naturally occurring delta-EEG enhancing nonapeptide in rabbits.European Journal of Physiology 369: 99–109. 1977.
Kovalzon VM and Strekalova TV. Delta sleep-inducing peptide (DSIP): a still unresolved riddle. Journal of Neurochemistry 97: 303–309. 2006.
Anders Bjartella; Rolf Ekmanb; Frank Sundlerc; Erik Widerlvd. Delta sleep-inducing peptide (DSIP): An overview of central actions and possible relationship to psychiatric illnesses. Nord J Psy, 42:2;111-117. 1988.
Endogenous sleep substances and sleep regulation. Utrecht, Netherlands: Japan scientific societies press, VNU science press. 1985.
Schoenenberger GA. Characterization, properties and multivariate functions of Delta-Sleep Inducing Peptide (DSIP). European Neurology 23: 321–345. 1984.
Iyer KS and McCann SM. Delta sleep inducing peptide (DSIP) stimulates the release of LH but not FSH via a hypothalamic site of action in the rat. Brain Research Bulletin 15: 535–538. 1987.
Kovalzon VM. DSIP: a sleep peptide or unknown hypothalamic hormone?. J. Evol. Biochem. Physiol. 30: 195–199. 1994.
Dragan Hrnia, Olivera Stanojlovia, Dragana ivanovia, Veselinka ušib. Delta-Sleep-Inducing Peptide Potentiates Anticonvulsive Activity of Valproate against Metaphit-Provoked Audiogenic Seizure in Rats. Pharmacology 2006;77:78-84.
Soyka M and Rothenhaeusler H. Delta Sleep-Inducing Peptide Opioid Detoxiﬁcation. Am. J. Psychiat. 154: 714–715. 1997.
 Schneider-Helmert D and Schoenenberger GA. The influence of synthetic DSIP (delta-sleep-inducing-peptide) on disturbed human sleep. Cellular and Molecular Life Sciences 37: 913–917. 1981.
Graf MV, Saegesser B, Schoenenberger GA. Degradation and aggregation of delta sleep-inducing peptide (DSIP) and two analogs in plasma and serum. Peptides. 1987 Jul-Aug;8(4):599-603.