Humoral transmission of sleep. IX. Activity and concentration of the sleep peptide delta in cerebral and systemic blood fractions.

1. In order to obtain information about production and activity of the "sleep factor delta", characterized as oligopeptide with MW approximately 860, the peptide concentration (in nM/g dry dialysate) and the EEG delta activity of the corresponding dialysate (delta percent and integral of delta increase) were determined for cerebral blood from the dural venous sinus, systemic blood from the femoral vein and cerebrospinal fluid (CSF) from sleeping and alert rabbit donors. 2. Before hypnogenic or walking stimulation all hemodialysates exhibit a basic peptide concentration (26 nM/g dry dialysate) and a corresponding basic delta activity (231 muV X sec delta integral within 6 sec). 3. The electric thalamic stimulation of donors, with parameters inducing orthodox delta-sleep, parallely increases the delta peptide concentration (160 nM/g) and its activity (543 muV X sec delta integral) in cerebral blood dialysate. 4. The cerebral blood plasma dialyzed in vitro after hypnogenic thalamic stimulation exhibits a still higher peptide concentration (197 nM/g) and delta activity (804 muV X sec), increased at will by using a steeper diffusion gradient in the dialyzer (possibility of extracting more peptide). 5. By contrast, the systemic femoral blood plasma, similarly dialyzed in vitro develops a weaker delta activity (646 muV X sec) than cerebral blood plasma, in spite of a higher peptide concentration (275 nM/g). This dissociation suggests an activity marked by concomittant waking factors added to the cerebral blood during passage through the hindlimbs musculature. 6. The fact that cerebral blood dialyzed in vivo in walking donors has no delta activity (-313 muV X sec) in spite of a minimal delta peptide concentration (10 nM/g) confirms the assumption that walking factors may mask the peptide activity. Additionally, it shows that they may also antagonize the peptide production. The sleep cycle seems to be regulated not only by neural, rapid acting antagonistic mechanisms, but also by humoral, slower acting antagonistic factors. 7. Cerebrospinal fluid withdrawn from sleeping donors induces insignificant changes in recipients, probably because of too small a peptide concentration in this fluid.