ISSN:0014-3022    

DOI:10.1159/000115708

出版商:S. Karger AG    

年代:1984

数据来源: Karger

ISSN:0014-3022    

DOI:10.1159/000115709

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

By means of light-microscopic autoradiography, binding sites for the delta sleep-inducing peptide (3H-DSIP) were observed on the soma and processes of cultured brain stem neurones but not on glial cells. Unlabelled DSIP at high concentrations inhibited binding of 3H-DSIP, indicating specific binding of this peptide. Our data suggest that brain stem neurones might possess receptors for the sleep-inducing peptide.

ISSN:0014-3022    

DOI:10.1159/000115710

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

From 1963 to 1970 the possibility of humoral transmission of delta (SWS)-EEG sleep in rabbits by, i.c.v. infusion of extracorporal dialysate from blood of the sinus confluens of donors kept asleep by electrical stimulation of the ventromedian intralaminar thalamus, has been established. From 1970 to 1977 we isolated, characterized and synthesized a nonapeptide called delta-sleep-inducing peptide (DSIP) responsible for this effect. Subsequently, intravenous administration of DSIP was shown to produce, in different animals, sleep lasting for hours. Analogs with exchanged amino acids in the sequence or shortening the peptide by one or two amino acids decreased or abolished the effect, as did breakdown products, suggesting a close structure-specificity. In contrast sleep-induction per se was found to be species specific, i.e. in cats REM-sleep was predominantly produced. I.c.v., i.v. and s.c. administration yielded, in contrast to pharmaka, a parabolic dose-response curve with different effective optima. Additionally to sleep-induction, DSIP acts upon the circadian rhythmicity of the locomotor activity and transmitter concentrations in the brain and on that of plasma proteins and Cortisol levels. We then synthesized a manyfold more powerful derivative by phosphorylation of the serine in position 7 (DSIP-P). Both forms, DSIP and DSIP-P occur in human CSF. Immunoreactive DSIP-like material was found in plasma of several mammals and humans, in human urine, CSF and milk. The penetration of the blood-brain barrier by the peptide has been proven and it was shown that unweaned rats are able to take up DSIP by the intestinal tract. The half-life time for proteolytic split-off of tryptophan by brain slices and homogenates is 15 min. Endogenous immunoreactive DSIP-like material in plasma, urine and CSF was found to be bound to a larger protein (carrier ?) and thus protected from proteo-

ISSN:0014-3022    

DOI:10.1159/000115711

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

The synthetic nonapeptide DSIP was studied in rabbits and cats under normal conditions and under conditions of disturbed sleep. In other experiments, the effect of the oligopeptide on withdrawal jumping provoked by naloxone in morphine-dependent mice was studied. In rabbits, DSIP at 25 µg·kg–1 i.v. and 1 mg·kg–1 s.c. augmented spindle-dominated, light nonREM sleep and prevented hyposomnia after a stressful situation. In cats, 25 µg·kg–1 i.v. and 100 µg·kg–1 s.c. preferentially augmented REM sleep and abolished the sleep suppressant effect of morphine. In morphine-dependent mice, 25.5 µg·kg–1 i.v. as well as doses beyond 85 µg·kg–1 s.c. attenuated naloxone-induced withdrawal jumping. In most experimental situations, indications for bell-shaped dose-response cur

ISSN:0014-3022    

DOI:10.1159/000115712

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

Repeated injections of delta sleep-inducing peptide (DSIP) were given to a 35-year-old male narcoleptic. Effects on wakefulness and sleep were evaluated by self-reports, performance tests, multiple sleep latency test and all-night polysomnography. DSIP reduced the frequency of sleep attacks and increased activity, alertness and performance during daytime. The sleep period was compressed by DSIP with enhancement of REM sleep. The results suggest that the effects are due to an accentuation of circadian and ultradian rhythms by DSIP.

ISSN:0014-3022    

DOI:10.1159/000115713

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

This paper summarizes different investigations into effects of delta sleep-inducing peptide (DSIP) injections on insomnia. Two different studies showed improvement of sleep following single injections of 25 nmol/kg b.w. before sleep. Repeated administrations indicated a buildup with normalization of sleep structure after four administrations. Repeated injections in the morning – besides increasing daytime activity – still had a strong positive effect on night sleep, but not so two doses daily. A case of insomnia in organic brain disease responded well to higher doses. The results are discussed as to the mode of action of DSIP and its possible therapeutic use in insom

ISSN:0014-3022    

DOI:10.1159/000115714

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

The hypothesis for this therapeutic use of delta sleep-inducing peptide (DSIP) was based on several animal studies conducted by Tissot. He showed that morphine, alcohol, pentobarbital as well as DSIP, when injected directly into the bulbo-mesencephalo-thalamic recruiting system, induced slow-wave sleep with numerous spindles. In all cases, this effect was reversed by Naloxone. Thus, it has been postulated that DSIP possesses an agonistic activity on opiate receptors and might be of value in the treatment of withdrawal syndromes. Therefore, DSIP was administered intravenously to 107 inpatients presenting with symptoms of alcohol (n = 47) or opiate (n = 60) withdrawal. The assessment of effect was based on the clinical evaluation by the physician and the nursing staff. Approximately 13% of the patients from the first and 22% from the second group did not fulfil the requirements for the evaluation of treatment. In, respectively, 97 and 87% of opiate and alcohol addicts, the clinical symptoms and signs disappeared after DSIP administration or improved markedly and rapidly. Anxiety, however, was slower to decrease. On the average, the clinical symptomatology had a more prolonged course and a higher number of DSIP injections were required for opiate addicts than for alcoholics. Tolerance to the DSIP treatment was good, aside from headaches reported by a few patients.

ISSN:0014-3022    

DOI:10.1159/000115715

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

Experimental results suggested a modulation or ‘programming’ interaction of delta sleep-inducing peptide (DSIP) with endogenous opioid-peptidergic systems and exogenous intracerebrally or systemically administered morphine and amphetamine. The induction of cerebral MAO-A activity, a pronounced influence on the circadian rhythms of locomotion and intracerebral neurotransmitter as well as plasma protein and Cortisol concentrations has been reported. DSIP was also shown to counteract experimentally induced stress situations in animals. An improvement of the psychomotor performance and the concentration capacity in humans beside sleep normalization and pronounced effects on withdrawal symptoms including pain states in alcoholics and opiate addicts was discovered. This encouraged a pilot study for a possible action of the peptide in humans suffering from chronic pronounced pain episodes. We investigated the therapeutic effect in 7 patients with migraine episodes and vasomotor headaches, chronic tinnitus and psychogenic pain attacks. The anamnestic (baseline) values were statistically compared with the katamnestic control period. DSIP lowered significantly the pain levels of 6 out of 7 patients after intravenous administration on 5 consecutive days followed by 5 injections every 48–72 h. Remarkably, a simultaneous significant reduction of the concomitantly occurring depressive states was obs

ISSN:0014-3022    

DOI:10.1159/000115716

出版商:S. Karger AG    

年代:1984

数据来源: Karger

ISSN:0014-3022    

DOI:10.1159/000210608

出版商:S. Karger AG    

年代:1908

数据来源: Karger