Delta sleep-inducing peptide

Pollard, B. J.1; Pomfrett, C. J. D.2
Author Information European Journal of Anaesthesiology: July 2001 - Volume 18 - Issue 7 - p 419-422


Delta sleep-inducing peptide (DSIP) is a naturally occurring substance, which was originally isolated from rabbit brain in 1977 [1]. This curious substance is a nonapeptide that is normally synthesized in the hypothalamus and targets multiple sites including some within the brainstem [2]. As its name suggests DSIP promotes sleep and this has been demonstrated in rabbits, mice, rats, cats and human beings [3–5]. In fact DSIP promotes a particular type of sleep which is characterized by an increase in the delta rhythm of the EEG.
DSIP is normally present in minute amounts in the blood. Brain and plasma DSIP concentrations exhibit a marked diurnal variation [6] and there has been shown to be a correlation between DSIP plasma concentrations and circadian rhythm in human beings. Concentrations are low in the mornings and higher in the afternoons. An elevation of endogenous DSIP concentration has been shown to be associated with suppression of both slow-wave sleep and rapid-eye-movement sleep and interestingly also with body temperature [7]. Plasma concentrations of DSIP are influenced by the initiation of sleep [8]. Patients with Cushing’s syndrome suffer from a lack of slow-wave sleep but the diurnal variation in slow-wave and rapid-eye-movement sleep in those patients appears to be similar to that in normal patients [9].
When compared with most other peptides, DSIP is unusual in that it can freely cross the blood–brain barrier and is readily absorbed from the gut without being denatured by enzymes [10,11]. DSIP is present in relatively high concentrations in human milk (10–30 ng mL–1). Any mother who has breast-fed her babies will attest to the ability of a feed to induce sleep. However, a feed of artificial milk may have a similar effect, and it is not known whether DSIP concentrations are related to the sleep–wake cycle in human neonates [12].
DSIP has been synthesized. Administration of the synthetic substance does not induce tolerance [13]. DSIP can be assayed by several techniques including radioimmunoassay (RIA), enzyme immunoassay and high-performance liquid chromatography with RIA [14–16]. DSIP has a half-life in human plasma of between 7 and 8 min [2]. It is degraded in blood, the pathway involving the amino-peptidases [17]. A potential drug interaction might therefore be envisaged between DSIP and drugs which inhibit or are themselves metabolized by peptidases. Captopril is one such agent and patients currently undergoing treatment with any of the angiotensin-converting enzyme inhibitors should probably be excluded from any DSIP treatment protocol until further studies have been undertaken.


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