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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    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.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The extracellular regulated kinases (ERK) 1 and ERK2 are members of mitogen-activated protein (MAP) kinase family that play an important role in transducing extracellular signals to the nucleus and have been implicated in a broad spectrum of biological responses. To test the hypothesis that MAP kinases may be involved in depression, we examined the activation of p44/42 MAP kinase and expression of ERK1 and ERK2 in the post-mortem brain tissue obtained from non-psychiatric control subjects (n = 11) and age- and the post-mortem interval-matched depressed suicide subjects (n = 11). We observed that p44/42 MAP kinase activity was significantly decreased in the prefrontal cortical areas (Brodmann's areas 8, 9 and 10) and the hippocampus of depressed suicide subjects without any change in the cerebellum. This decrease was associated with a decrease in mRNA and protein levels of ERK1 and ERK2. In addition, the expression of MAP kinase phosphatase (MKP)2, a ‘dual function’ ERK1/2 phosphatase, was increased in the prefrontal cortex and hippocampus. These studies suggest that p44/42 MAP kinases are less activated in the post-mortem brain of depressed suicide subjects and this may be because of reduced expression of ERK1/2 and increased expression of MKP2. Given the role of MAP kinases in various physiological functions and gene expression, alterations in p44/42 MAP kinase activation and expression of ERK1/2 may contribute significantly to the pathophysiology of depressive disorders.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 448 (1985), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 448 (1985), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1435-1463
    Keywords: Chronic haloperidol ; chronic clozapine ; dose-response ; oral dyskinesias ; tardive dyskinesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Whether the pathophysiology and treatment of neurolepticinduced oral dyskinesias in rats parallel that for tardive dyskinesia in humans remains a question. To address the issue further, Sprague Dawley rats were treated for 6 months with multiple oral doses of haloperidol (1.5 and 3.0 mg/ kg/day) or clozapine (10, 20, and 30 mg/kg/day) and compared with water treated animals. The rate of oral dyskinesias was monitored at study start and monthly by trained raters who were blind to treatment group. All haloperidoltreated rats developed oral dyskinesias at a significantly higher rate than rats treated with water (p=0.0007) or those treated with clozapine (p=0.0017). Each dose of haloperidol produced significantly higher rates of oral dyskinesias than did any dose of clozapine and did so in an apparent dose-sensitive manner. Clozapine lacked a dose-sensitive relationship with the oral dyskinesias, and failed to show a significant difference in rate from control rats at any dose. Plasma levels of haloperidol with these doses were in the human therapeutic range; with clozapine only the highest dose produced plasma levels in the human therapeutic range. These data show little association between rat oral dyskinesias and clozapine treatment, whereas a strong association is present with haloperidol. The data are, thereby, consistent with the clinical association of tardive dyskinesia with typical neuroleptics like haloperidol but not with the atypical neuroleptic clozapine.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 71 (1988), S. 159-163 
    ISSN: 1435-1463
    Keywords: dopamine receptors ; SKF 38393 ; prolactin ; growth hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary SKF 38393, a selective D-1 dopamine receptor agonist, elevated plasma prolactin levels in eight patients with various neurological disorders. Growth hormone concentrations were unaffected by SKF 38393 administration. The results suggest that D-1 receptors may be involved in the regulation of prolactin secretion.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 66 (1979), S. 239-242 
    ISSN: 1432-2072
    Keywords: Schizophrenia ; Dopamine ; Ergot derivatives ; Bromocriptine ; CF 25-397
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Seven neuroleptic-free schizophrenic patients received bromocriptine and eight schizophrenic patients received CF 25-397, both ergot derivatives with dopamine agonist activity. Psychosis failed to improve in response to either drug at the relatively low doses administered. Unlike the antipsychotic property of apomorphine at low dose levels, neither of these ergot drugs improved schizophrenic symptomatology.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-2072
    Keywords: Animal model ; Tardive dyskinesia ; Chronic haloperidol ; Rat strains ; Neuroleptic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Vacuous chewing movements (VCMs) in three different rat strains developed at considerably different rates after 19 weeks of continual haloperidol treatment at an average daily dose of 1.5 mg/kg. Sprague Dawley (SD) rats displayed relatively high rates of VCMs with low variability, compared to Wistar (W) and Long Evan (LE) rats. Atropine decreased but did not abolish VCMs in two of the three strains (LE〉SD). After haloperidol withdrawal, VCMs remitted gradually in all strains, but least rapidly in the SD rats. In a separate group of SD rats, VCMs were rated weekly from the start of haloperidol treatment and showed considerable interindividual variability. Even after 24 weeks of continuous haloperidol, 12 out of 32 treated rats showed no VCMs at all, while 13 out of 32 had intense movements, analogous to the clinical situation in which only some patients treated with neuroleptics develop tardive dyskinesia. These results indicate that there are individual and strain differences in the development of VCMs, and suggest that there may also be genetically determined differences in the development of tardive dyskinesia.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2072
    Keywords: Key words Tardive dyskinesia ; Mixture analysis ; Chronic haloperidol ; Rats ; Vacuous chewing movements
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Spontaneous adventitious oral movements which are produced in rats by very chronic (6- month) neuroleptic treatment have some phenomenologic and pharmacologic characteristics in common with tardive dyskinesia in humans. However, since not all of the features match, this putative model has been questioned and further support is warranted. Data from several laboratories support dichotomizing these neuroleptic-induced rat oral movements into “low”or “not TD-like” movements and “high”or “TD-like” movements, similar to the division of neuroleptic-induced involuntary movements in humans. Here, we have used mixture analysis to test this proposal statistically in 185 haloperidol-treated and 127 water-treated animals. Rats from several different studies were grouped together to form these two cohorts. The haloperidol dose, route of administration, rating technique, and balanced experimental groups were held constant across all experiments. Results show that two distinct groups of rat movements are induced by very chronic haloperidol treatment (1.5 mg/kg per day). The “low” vacuous chewing movement (VCM) group of rats had an average of 3.6 VCMs/5 min, and the “high” VCM group had an average of 16.1 VCMs/5 min; the conrol group, with a median VCM rate of 2.0 VCMs/5 min, demonstrated a single distribution. These data suggest that rats, like humans, dichotomize into two groups either expressing or not expressing “high” VCM dyskinesias with very chronic haloperidol treatment.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-2072
    Keywords: Cholecystokinin ; Schizophrenia ; Peptide pharmacology ; Caerulein ; Cerebrospinal fluid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neuroleptic-free schizophrenic patients received caerulein, a potent analogue of cholecystokinin octapeptide, in a fixed- and rising-dose schedule. In addition, neuroleptic-treated patients received a single dose of the peptide with a 4-week follow-up. No significant change in mental status was observed after any of these administration schedules. Peak plasma levels of caerulein were noted at 20–30 min after IM administration; at this time no changes in cortical evoked potential were demonstrated. Furthermore, levels of cholecystokinin were not found to be reduced, but were in fact elevated in lumbar cerebrospinal fluid of schizophrenic patients. These data argue against the antipsychotic efficacy of systemic caerulein administration and, because evidence of CNS response to CCK is lacking, suggest that other pharmacologic strategies may be necessary to effectively modify central peptide systems with systemically administered drugs.
    Type of Medium: Electronic Resource
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