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-

This content is only available via PDF.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.