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Notes: Abstract: Cholecystokinin octapeptide (CCK26–33) is metabolized by neural membranes with an initial cleavage to CCK29–33 and subsequent breakdown to CCK31–33 and CCK32–33; this pattern of proteolysis occurs on incubation with either P2 or purified lysed synaptosomal membranes. To determine whether the pattern of CCK26–33 proteolysis is unique to the brain and whether regional brain differences in its pathway or rate exist, we analyzed the proteolysis of CCK by synaptic membranes of various brain areas and cellular membranes of peripheral tissue. The pattern of degradation in brain did not differ among the regions studied. The overall proteolysis rate, as measured by the formation of tryptophan, was higher in the striatum than in the cortex, although CCK29–33 was formed at the same rate in both areas. In nonneural tissue, the rate of degradation was highest in liver membranes and lowest in pancreatic acinar cell preparations. Thus, it appears that degradative peptidases are not necessarily colocalized with CCK receptors. The pattern of product formation is the same in peripheral compared with CNS membranes; thus, the degradative pathway does not appear to be unique to brain tissue. The enzyme present in synaptic membranes that is responsible for CCK29–33 formation requires a metal ion and sulfydryl groups for the catalysis and thus is a metalloendopeptidase. Furthermore, its activity is inhibited by Ac-Gly-Phe-Nle-al, a peptide aldehyde whose sequence bears some homology to the amino acid sequence in the region of CCK26–33 that is cleaved by this enzyme.

Notes: Summary Preclinical evidence suggests that the D-1 dopamine receptor contributes to the generation of behaviors used as models for human extrapyramidal disorders. To evaluate the potential of D-1 receptor stimulation in neurologic disease, SKF 38393, a selective D-1 dopamine receptor agonist, was administered to seven patients with idiopathic Parkinson's disease in a double-blind, placebo controlled study. SKF 38393 was found to be rapidly absorbed when administered orally, and to occur in micromolar concentrations in spinal fluid. No change in scores of parkinsonian severity were noted when SKF 38393 was administered alone, or when the drug was combined with intravenous levodopa. The results support the view that the pathophysiology of Parkinson's disease may relate exclusively to the D-2 subclass of dopamine receptors.

Notes: Zusammenfassung Die elektronenmikroskopische Untersuchung zeigte in beiden Gruppen ähnliche Veränderungen des endoplasmatischen Reticulums, des Golgi-Apparates und der perikanaliculären Zone mit intracellulärer Anhäufung von Galle. Da weder obstruierende, noch entzündliche Veränderungen an den Gallengängen, noch Gallethromben in den Gallecapillaren beobachtet werden konnten, wird angenommen, daß die nachgewiesene intracelluläre Cholostase auf eine primäre Beeinträchtigung des cellulären Sekretionsmechanismus zurückgeht. Die Befunde stimmen mit der Hypothese überein, daß der chronische idiopathische Ikterus auf ein Hindernis bei der Ausscheidung des Bilirubins durch die Leberzellen in die Gallecapillaren zurückzuführen ist. Diese Fälle wären zu definieren als rein intracelluläre Cholostase auf dem Boden eines primären Leberzellschadens.

Notes: Summary 1. Unit activity was recorded in the prefrontal cortex of Rhesus monkeys during performance of a delay task with two motor components, an ocular saccade and an arm movement, following a complex pattern of auditory and visual stimuli. A special feature of the paradigm was that onsets of the different sensory stimuli, orienting saccade and arm movement were dissociated in time at predetermined time intervals. 216 task-related units were recorded. Discussion of the data focuses on two groups of cells the activity of which is modified by the saccade: the signal-related presaccadic tonic cells and the post-saccadic tonic cells. 2. Activity of signal-related pre-saccadic tonic cells was initiated with the onset of peripheral stimuli, visual and/or auditory, and terminated with an orienting saccade. Spatial selectivity was a feature of most units. They seemed to encode the region of space cued by the stimulus. 3. Many units were visually responsive. Activation of these depended both upon retinal locus of the stimulus and the requirement they imposed on subsequent behavior. Termination of their activity demanded foveation of some visual targets, not necessarily the one which had initiated their response. 4. The majority of these signal-related pre-saccadic tonic cells responded to onset of auditory stimuli. The termination of tonic activity in these cells with foveation of the region in space from which the signal originated suggests a spatial memory process that is no longer used when the visual fixation response can signal equivalent spatial information. 5. Post-saccadic tonic cells were activated as the animals fixated a target; spatial selectivity was a feature of most of these. We suggest that this group of cells are part of the system which encodes the location of a target only if it is the goal of a visually guided movement. 6. A substantial proportion (20–30%) of signal-related tonic cells and post-saccadic tonic cells were activated differentially by use of one arm versus the other. These cells appeared to be more directly involved in motor preparation.

Notes: Summary 1. Single neuron activity was recorded from the prefrontal cortex of two macaque monkeys during the performance of a task involving spatial sequencing. The monkeys faced a panel displaying a central fixation point and three fixed targets (two lateral and one above the point of fixation). In the first phase of each trial, the three targets were turned on in random order: in the second phase, the animal had to press each target, still lighted, in the order of their illumination. Thus, successful performance of the task depended strongly on temporal memory. The animals were fitted with DC-EOG electrodes. 2. Three hundred and two task-related neurons were recorded in the superior arcuate area and caudal part of sulcus principalis. Among the cells whose pattern of activity appeared to be related to the sequencing task, five classes were distinguished: Visual tonic (VT), fixation, context, saccade related and visual phasic cells. In addition, a small number of cells appeared to be related to other aspects of the behavior, but not to the sequencing task. Our present analysis concentrates on two groups of sequencing task-related cells (VT and context cells). 3. The VT cells (35/302-11.5%) were recorded exclusively from the superior arcuate area. All VT cells increased their firing rate (sustained activation) during fixation of the central fixation point (FP) following onset of one of the three targets used, specific for a given cell (directional or spatial selectivity). In one group of VT cells, a shift in the eye position towards the specific peripheral target resulted in the return of the cells' firing rate to the pre-trial level. In the other group of VT cells, reset of the firing rate to pre-trial level was not related to the onset of fixation of the peripheral target. Sustained activation of the VT cells depended also on the sequential order of illumination of the specific target (temporal selectivity). In twenty-four cells (68.5% of VT cells) sustained activation was observed when the target came first in the sequence. Onset of the target in the second or third rank elicited either no response or only a short lasting phasic activation. In the remaining eleven cells (31.5% of VT cells), sustained activation was only observed when the target came second in a given sequence. The firing of the VT cells was correlated with the animals' performance of the task. On trials where the animals selected successive targets in an incorrect order, the temporal pattern of activation of VT cells was different from that in the correctly performed trials. Thus, the correct temporal encoding of a target appeared to be a prerequisite for the correct performance of a sequence. 4. The context cells (36.5%-16/302) were activated when the animal fixated a particular target during execution of the sequence and, like VT cells, were encountered exclusively in the penetrations through the superior arcuate area. Activation also depended on the state (illuminated vs extinguished or hit vs non-hit) of the non-fixated targets and/or on their time-relationships with respect to the fixated target hence context cells. 5. Properties of VT and context cells revealed in the present experiment are consistent with the idea that the superior arcuate area is involved in temporally and spatially extended structures of behavior. If so, the arcuate area would constitute a specialized part of prefrontal cortex implicated in construction of oculomotor plans.