Delta sleep‐inducing peptide (DSIP): a still unresolved riddle

Abstract

Delta sleep-inducing peptide (DSIP) was isolated from rabbit cerebral venous blood by Schoenenberger-Monnier group from Basel in 1977 and 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 DSIP gene, protein and possible related receptor. Thus the hypothesis regarding DSIP as a sleep factor is extremely poorly documented and still weak. Although DSIP itself presented a focus of study for a number of researchers, its natural occurrence and biological activity still remains obscure. DSIP 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 DSIP biological activity. This assumption is based on: (i) a highly specific distribution of DSIP-like immunoreactivity in the neurosecretory hypothalamic nuclei of various vertebrate species that are not particularly relevant for sleep regulation, as revealed by the histochemical studies of the Geneva group (Charnay et al.); (ii) a large spectrum of DSIP biological activity revealed by biochemical and physiological studies in vitro; (iii) significant slow-wave sleep (SWS) promoting activity of certain artificial DSIP structural analogues (but not DSIP itself!) in rabbits and rats revealed by our early studies; and (iv) significant SWS-promoting activity of a naturally occurring dermorphin-decapeptide that is structurally similar to DSIP (in five of the nine positions) and the sleep-suppressing effect of its optical isomer, as revealed in rabbits. Potential future studies are outlined, including natural synthesis and release of this DSIP-like peptide and its role in neuroendocrine regulation.

The Effects of Caffeine on Sleep inDrosophilaRequire PKA Activity, But Not the Adenosine Receptor

“…However, the precise mechanisms by which adenosine exerts its somnogenic activity remain unclear. Much of the evidence for a sleep-promoting role of adenosine comes from pharmacological studies (Porkka-Heiskanen et al, 2002), but a variety of physiological substrates can, like adenosine, induce sleep (Ueno et al, 1983; Krueger et al, 1984; Shoham et al, 1987; Kovalzon and Strekalova, 2006; Krueger, 2008). …”

Modulatory effects of delta sleep-inducing peptide in a lindane model of generalized seizures

“…DSIP is a natural and ubiquitous somnogenic nonapeptide, which has no side effects even at very high doses. DSIP takes part in numerous non-sleep related physiological functions; its antiepileptic role [30,31] was of most interest to us. In our laboratory, we examined DSIP as an anticonvulsive neuropeptide in metaphit (1-(1(3-isothiocyanatophenyl)-cyclohexyl (piperidine)audiogenic epilepsy [30].…”

Delta sleep‐inducing peptide and glucocorticoid‐induced leucine zipper: potential links between circadian mechanisms and obesity?

“…demonstrated that the serum levels of DSIP in rats exhibited a diurnal oscillatory expression profile, implicating a link between DSIP and circadian mechanisms (30). A wealth of literature has demonstrated that DSIP is associated with sleep induction and behaviour in mammals (reviewed in (31–33)). Furthermore, a limited number of human and rodent studies have found that the administration of DSIP analogues protects against weight gain and diabetes in elderly subjects (34,35).…”

“…Furthermore, a limited number of human and rodent studies have found that the administration of DSIP analogues protects against weight gain and diabetes in elderly subjects (34,35). Nevertheless, research on DSIP has been stymied because of the fact that its parent protein and encoding gene remain unknown (33).…”

“…In most studies, the detection of DSIP has depended on the use of antibody reagents (31–33). In addition to DSIP, these antibodies were found to recognize an associated DSIP Immunoreactor protein present in multiple tissues throughout the body.…”