THE DELTA SLEEP-INDUCING PEPTIDE (DSIP):

still unresolved riddle

 

KovalzonV.M., Strekalova T.V.

 

Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences, Moscow, Central Institute of Mental Health, Mannheim, Germany

e-mail: V.M.Kovalzon, kovalzon@sevin.ru

 

DSIP (Delta Sleep-lnducing Peptide), a nonapeptide with a unique ammo acid sequence (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu), was isolated from cerebral venous blood of rabbits subjected to low-frequency ("hypnogenic") electro-stimulation of intralaminar thalamic nuclei (the so-called "trophotropic areas", according to W.Hess) by Shoenenberger-Monnier group from Basel in 1977 and still regarded as one of the most enigmatic regulatory peptides. DSIP bibliography includes about 2000 references and generally two points of view are present: “optimistic” and “skeptical”. The first of them is based upon extensive investigations carried out in a number of different laboratories for a period of almost 3 decade which demonstrated that DSIP or some DSIP-like peptide(s) is present in free and bound forms in various cerebral structures, primarily the hypothalamus and limbic system, as well as pituitary and different peripheral organs, tissues and body fluids, where it colocalizes with several peptide and non-peptide neurotransmitters. Endogenous DSIP (DSIP-like peptide) takes part in a large spectrum of both physiological and pathological processes including stressful, painful, immune, hormonal, thermoregulatory, regulation of circadian rhythmicity, alcohol and opiate dependency formation, etc. So in accordance to the “optimistic” view, DSIP is regarded as a molecule of the paramount importance which probably plays a role of the internal stress-limiting factor in mammal body. “Skeptical” view on the natural occurrence of DSIP is based upon the following items: (1) the lack of detection of DSIP gene, precursor protein, specific receptor and receptor gene; (2) the lack of detection of DSIP amino-acid sequence in DSIP-like immunoreactive material. Criticism on DSIP biological activity is based upon a number of results which do not confirm some previous data on such activity at least in vivo, and especially on sleep. We hypothesize yet the existence of another still unknown peptide(s) which structure is similar though not identical to that of the DSIP and which is responsible (at least partly) for its biological activity. Such assumption is based on: (i) highly specific distribution of DSIP-like immunoreactivity in the neurosecretory hypothalamic nuclei of various vertebrate species, revealed by sophisticated histochemical studies of Geneva team (Charnais 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 the certain artificial DSIP structural analogs in rabbits and rats revealed by our early studies; (iv) significant SWS promoting activity of naturally occurring dermorphin-decapeptide structurally similar to DSIP (in 5 of the 9 positions) and sleep-suppressing effect of its artificial optical isomer, revealed in rabbits; (v) significant increase in SWS which follows combined administration of DSIP together with some other peptides: DSIP+NPY, DSIP+NPY+CGRP, DSIP+NPY+ANP in rabbits. Perspective of future studies is outlined. Supported by grants from RFFI (02-04-48318a) and RHSF (04-06-00242a).

 

Дельта-Сон Индуцирующий Пептид (ДСИП): нерешенная загадка

Ковальзон В.М., Стрекалова Т.В.

Институт проблем экологии и эволюции РАН, Москва, и Центральный Институт психического здоровья, Мангейм, Германия