Structure-activity relationship in the effects of delta-sleep-inducing peptide (DSIP) on rat sleep

Obál, F.; Kovalzon, V. M.; Kalikhevich, V. N.; Török, Angela; Alföldi, P.; Sáry, Gyula; Hajós, Mihály; Penke, Botond

doi:10.1016/0091-3057(86)90432-6

Cited by 12 publications

(4 citation statements)

References 20 publications

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“…Some research suggests that DSIP acts indirectly on sleep by modulating circadian rhythms (11) or by reducing stress (12). Our own experiments suggest that DSIP analogs that are resistant to enzymatic breakdown may enhance a pre-existing sleep process, but DSIP per se does not promote sleep in the rat (13). Furthermore, the antibodies to DSIP may cross-react with proteins not implicated in sleep regulation (14).…”

Section: Introductionmentioning

confidence: 87%

Biochemical regulation of non-rapid-eye-movement sleep

Obál

Krueger²

2003

Front Biosci

274

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The concept, that sleep regulatory substances (sleep factors) exist, stems from classical endocrinology and is supported by positive transfer experiments in which tissue fluids obtained from sleepy or sleeping animals elicited sleep when injected into recipient animals. The transfer experiments concluded with the identification of four sleep factors: delta sleep-inducing peptide (DSIP), uridine, oxidized glutathione, and a muramyl peptide. A physiological sleep regulatory role, however, has not been determined for these substances. In contrast, transfer experiments did not play a part in the development of the strong experimental evidence that implicated the currently known sleep factors in sleep regulation. These substances include adenosine, prostaglandin D2 (PGD2), growth hormone-releasing hormone (GHRH), interleukin-1 (IL1) and tumor necrosis factor (TNF). They promote non-REMS in various species, inhibition of their action or endogenous production results in loss of spontaneous sleep, and their synthesis and/or release display variations correlating with sleep-wake activity. Although the source of these substances vary they all enhance sleep by acting in the basal forebrain/anterior hypothalamus--preoptic region. It is also characteristic of these substances that they interact in multiple ways often resulting in mutual stimulation or potentiation of each other. Finally, there is a third group of substances whose significance in sleep regulation is less clear but for which there are two or more lines of evidence suggesting that they may have a role in modulating non-REM sleep (NREMS). This group includes oleamide, cortistatin, cholecystokinin (CCK), insulin, and nitric oxide (NO). More sleep regulatory substances are likely to be discovered in the future although it is a long and difficult process requiring multiple laboratories to generate sufficient convincing data to implicate any one of them in sleep regulation.

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Section: Introductionmentioning

confidence: 87%

Biochemical regulation of non-rapid-eye-movement sleep

Obál

Krueger²

2003

Front Biosci

274

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“…A number of studies failed to confirm SWS‐ or PS‐promoting properties of DSIP, as well as an increase in the EEG spectrum delta power, after either introcerebroventricular (ICV) or systemic administration of DSIP; only minor effects were found in others, and even an impairment of sleep has been reported (Schneider‐Helmert and Shoenenberger 1983; Obál et al . 1985; Kovalzon 1986, 1994, 1999; Obál et al . 1986; Borbely and Tobler 1989; Inoué 1989; Elkafi et al .…”

Section: Structure Of Delta Sleep‐inducing Peptide (Dsip) and Dermorpmentioning

confidence: 99%

“…This means that the increase in DSIP molecule resistance against aminopeptidase degradation did lead to the clear appearance of its functional (sleep‐promoting) activity in vivo . These data were obtained in joint totally blind studies of the Russian, Hungarian and Japanese researchers of the late 1980s (Obál et al . 1986; Kimura‐Takeuchi et al .…”

Section: Structure Of Delta Sleep‐inducing Peptide (Dsip) and Dermorpmentioning

confidence: 99%

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

Kovalzon

Strekalova

2006

Journal of Neurochemistry

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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.

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“…However, two of the analogues did induce sleep but one produced arousal. It would appear therefore that there might be the potential for not only sleep but sleep reversal within the analogues of DSIP [42].…”

Section: Clinical Usesmentioning

confidence: 99%