Delta sleep inducing peptide

Delta sleep inducing peptideDSIP) basic information:

Synonym:DSIP,Emideltide,Sleep inducing Peptide


CAS number:62568-57-4

Molecular weight:848.81


Delta sleep-inducing peptide,abbreviated DSIP,Swiss Schoenenberger-Monnier group who isolated it from the cerebral venous blood of rabbits in an induced state of sleep first discovered it in 1974.

Meanwhile,he found It is in both free and bound forms in the hypothalamus,limbic system and pituitary as well as various peripheral organs, tissues and body fluids.[3] In the pituitary it co-localises with many peptide and non-peptide mediators such as corticotropin-like intermediate peptide (CLIP), adrenocorticotrophic hormone (ACTH), melanocyte-stimulating hormone (MSH), thyroid-stimulating hormone (TSH) and melanin concentrating hormone (MCH). It is abundant in the gut secretory cells and in the pancreas where it co-localises with glucagon.[4]

In addition,In the brain its action may be mediated by NMDA receptors.[5]

It is unknown where Delta sleep-inducing peptide 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.[6] 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,[7] but as yet no structure or gene has been found for this precursor.

However,evidence supports the current belief that it is regulated by glucocorticoids.[8]

Gimble et al. suggest that Delta sleep-inducing peptide interacts with components of the MAPK cascade and is homologous to glucocorticoid-induced leucine zipper (GILZ).[9]GILZ can be induced by Dexamethasone.It prevents Raf-1 activation, which inhibits phosphorylation and activation of ERK. See [1] for image showing the pathway analysis of DSIP [10]

It initially regarded as a candidate sleep-promoting factor. However, the link between DSIP and sleep has never been further characterized, in part because of the lack of isolation of the Delta sleep-inducing peptide gene, protein and possible related receptor. Thus the hypothesis regarding DSIP as a sleep factor is extremely poorly documented and still weak. Although Delta sleep-inducing peptide itself presented a focus of study for a number of researchers, its natural occurrence and biological activity still remains obscure.After that, Delta sleep-inducing peptide structure is different from any other known representative of the various peptide families. In this mini-review we hypothesize the existence of a DSIP-like peptide(s) that is responsible (at least partly) for DSIP-like immunoreactivity and Delta sleep-inducing peptide  biological activity.

Roles in endocrine regulation

  1. Decreases basal corticotropin level and blocks its release.[13]
  2. Stimulates release of luteinizing hormone (LH).[14]

 3.Stimulates release of somatoliberin and somatotrophin secretion and inhibits somatostatin secretion.[15]

Roles in physiological processes

  1. Can act as a stress limiting factor.[16][17][18]

 2.May have a direct or indirect effect on body temperature and alleviating hypothermia.[19][20][21]

 3.Can normalize blood pressure and myocardial contraction.[22].[23]

  1. It has been shown to enhance the efficiency of oxidative phosphorylation in rat mitochondria in vitro, suggesting it may have antioxidant effects.[24]

 5.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[25][26] and suppression of paradoxical sleep, (PS)[27][28] while some studies show no correlation.[29] Stronger effects on sleep have been noted for the synthesized analogues of Delta sleep-inducing peptide.[30]

  1. It may have an impact on human lens epithelial cell function via the MAPK pathway, which is involved in cell proliferation, differentiation, motility, survival, and apoptosis.[31]

1.Schoenenberger GA, Maier PF, Tobler HJ and Monnier M (1977). “A naturally occurring delta-EEG enhancing nonapeptide in rabbits”. European Journal of Physiology

2.Kovalzon VM and Strekalova TV (2006). “Delta sleep-inducing peptide (DSIP): a still unresolved riddle”. Journal of Neurochemistry

3.Charnay Y, Bouras C, Vallet PG, Golaz J, Guntern R, Constantinidis J (1989). “Immunohistochemical distribution of delta sleep inducing peptide in the rabbit brain and hypophysis”. Neuroendocrinology

4.Kovalzon VM and Strekalova TV (2006). “Delta sleep-inducing peptide (DSIP): a still unresolved riddle”. Journal of Neurochemistry

5.Sudakova KV, Umriukhina PE, Rayevskyb KS (2004). “Delta-sleep inducing peptide and neuronal activity after glutamate microiontophoresis: the role of NMDA-receptors”. Pathophysiology

6.Schoenenberger GA (1984). “Characterization, properties and multivariate functions of Delta-Sleep Inducing Peptide (DSIP)”. European Neurology

7.Endogenous sleep substances and sleep regulation. Tokyo and BV, Utrecht, Netherlands: Japan scientific societies press, VNU science press. 1985. 

8.Westrin A, Ekman R, and Traskman-Bendz L (1998). “High Delta Sleep-Inducing Peptide-Like Immunoreactivity in Plasma in Suicidal Patients with Major Depressive Disorder”. Biological Psychiatry

9.Gimble JM, Ptitsyn AA, Goh BC, Hebert T, Yu G, Wu X, Zvonic S, Shi X-M and Floyd ZE (2009). “Delta sleep-inducing peptide and glucocorticoidinduced leucine zipper: potential links between circadian mechanisms and obesity?”. Obesity reviews

10.The Association for Research in Vision and Ophthalmology, Inc. (2007)

11.synthesized by V. N. Kalikhevich and S. I. Churkina, University Chemical Institute, St. Petersburg, Russia, and I. I. Mikhaleva and I. A. Prudchenko, Institute of Bio-organic Chemistry, Russian Academy of Sciences, Moscow

12.Charnay Y, Golaz J, Vallet PG, Bouras C (1992). “Production and immunohistochemical application of monoclonal antibodies against delta sleep-inducing peptide”. J Chem Neuroanat  

13.Schoenenberger GA (1984). “Characterization, properties and multivariate functions of Delta-Sleep Inducing Peptide (DSIP)”. European Neurology   

14.Iyer KS and McCann SM (1987). “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.Kovalzon VM (1994). “DSIP: a sleep peptide or unknown hypothalamic hormone?”. J. Evol. Biochem. Physiol.

16.Stress: Neuroendocrine and Molecular Approaches. Amsterdam: Gordon and Breach Science Publishers. 1992.

17.Sudakova KV, Coghlan JP, Kotov AV, Salieva RM, Polyntsev YV, Koplik EV (1995). “Delta-sleep inducing peptide sequels in mechanisms of resistance to emotional stress”. Ann. N.Y. Acad. Sci.

  1. Khvatova EM, Samartzev VN, Zagoskin PP, Prudchenko IA, Mikhaleva II (2003). “Delta sleep inducing peptide (DSIP): effect on respiration activity in rat brain mitochondria and stress protective potency under experimental hypoxia”.

19.Pollard BJ and Pomfrett CJD (2001). “Delta sleep-inducing peptide”. Eur. J. Anaesthesiol.

  1. Yehuda S, Kastin AJ and Coy DH (1980). “Thermoragulatory and locomotor effects of DSIP: paradoxical interaction with d-amphetamine”. Pharmacol. Biochem. Behav.

21.Yehuda S and Mostofsky DI (1984). “Modification of the hypothermic circadian cycles induced by DSIP and melatonin in pinealectomized and hypophysectomised rats”.

22.Schoenenberger GA (1984). “Characterization, properties and multivariate functions of Delta-Sleep Inducing Peptide (DSIP)”. European Neurology

  1. Yehuda S and Carasso R (1988). “DSIP – a tool for investigating the sleep onset mechanism: a review”. International J. Neurosci.
  2. Khvatova EM, Samartzev VN, Zagoskin PP, Prudchenko IA, Mikhaleva II (2003). “Delta sleep inducing peptide (DSIP): effect on respiration activity in rat brain mitochondria and stress protective potency under experimental hypoxia”.
  3. Iyer KS, Marks GA, Kastin AJ, and McCann SM (1988). “Evidence for a role of delta sleep-inducing peptide in slow-wave sleep and sleep-related growth hormone release in the rat”. Proc Natl Acad Sci U S A

26.Susić V, Masirević G, Totić S (1987). “The effects of delta-sleep-inducing peptide (DSIP) on wakefulness and sleep patterns in the cat”. Brain Research

27.Seifritz E, Muller M, Schonenberger G, Trachsel L, Hemmeter U, Hatzinger M, Ernst A, Moore P and Holsboer-Trachsler E (1995). “Human plasma DSIP decreases at the initiation of sleep at different circadian times”. Peptides

28.Steiger A and Holsboer F (1997). “Neuropeptides and human sleep”.

  1. Nakagaki K, Ebihara S, Usui S, Honda Y, Takahashi Y, Kato N (1986). “Effects of intraventricular injection of anti-DSIP serum on sleep in rats”. Yakubutsu Seishin Kodo (Japanese journal of psychopharmacology)

30.Kovalzon VM (2001). “Sleep-Inducing Properties of DSIP Analogs: Structural and Functional Relationships”. Biology Bulletin

31.Gupta V, Awasthi N and Wagner BJ (2007). “Specific Activation of the Glucocorticoid Receptor and Modulation of Signal Transduction Pathways in Human Lens Epithelial Cells”. Investigative Ophthalmology and Visual Science

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