Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analysis of silver stained two-dimensional (2D) gels of cerebrospinal fluid (CSF) from 27 patients with schizophrenia (SCZ) and 10 patients with Alzheimer's disease (AD) revealed an increase in the relative amount of a polypeptide of 18,000M(r) and isoelectric point of 6.5 when compared to the appropriate controls. This protein was identified by its electrophoretic characteristics and by immune analysis of Western blots as an isoform of alpha-2 haptoglobin, provisionally identified as alpha-2FS haptoglobin. Alzheimer's disease versus control CSF samples showed a 6.8-fold increase in the percent mean density value of this haptoglobin isoform (n = 10 AD vs 11 control; P > 0.025) while a 4.4-fold increase was observed in the schizophrenic patients (n = 17 SCZ vs 10 control; P > 0.001). Two additional polypeptides (proteins '127' and '128') of 40,000 M(r) and isoelectric points 5.7 and 5.9, respectively, described previously by this laboratory, were found in the CSF of 27% of schizophrenics, 23% of the Alzheimer's disease patients, and 4% of the controls in the current study. The presence of proteins 127 and 128, as well as the increased concentrations of alpha-2 haptoglobin in the CSF of Alzheimer's disease and schizophrenic patients, may be useful as diagnostic biological markers. They may also indicate a common pathophysiology between these diseases.
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PMID:Cerebrospinal fluid protein variations in common to Alzheimer's disease and schizophrenia. 128 67

We have studied the effects of psychotropic drugs on patterns of protein synthesis in human lymphomononuclear cells by two-dimensional gel electrophoretic analysis. Drugs effective in treatment of schizophrenia specifically increased the relative synthesis of a 30-kDa polypeptide in cultured human lymphomononuclear cells whereas dopamine (DA) or psychoactive drugs lacking antipsychotic properties did not. The effect was stereospecific with respect to the clinically active and inactive isomers of flupenthixol. Synthesis of the 30-kDa polypeptide appears therefore to be correlated with antipsychotic properties but not with DA receptor binding. It is possible that such effects may be associated with the clinically beneficial effect of antipsychotic drugs in the brain.
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PMID:A specific effect of antipsychotic drugs on protein synthesis in human lymphomononuclear cells. 197 Oct 8

The neuronal dopamine transporter/uptake site can be covalently labeled with the photoaffinity probe 1-(2-[bis-(4-fluorophenyl) methoxy]ethyl)-4-[2-(4-azido-3-[125I]iodophenyl)ethyl]piperazine [( 125I]FAPP) and visualized following sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography. Upon photolysis, [125I]FAPP specifically incorporated into a polypeptide of apparent Mr = 62,000 in membranes from both the putamen and the caudate nucleus of control, Alzheimer's, schizophrenia, and Huntington's diseased brain, and following complete deglycosylation, migrated as an Mr approximately 48,000 polypeptide. In parkinsonian postmortem putamen, however, there was no detectable photoincorporation of [125I]FAPP into the ligand binding subunit of the dopamine transporter. [125I]FAPP did specifically label the Mr 62,000 polypeptide of parkinsonian caudate, although with efficiencies of 20-50% of control. The asymmetrical loss of the dopamine transporter in Parkinson's diseased striatum was confirmed in reversible receptor binding experiments using [3H]GBR-12935 (3H-labeled 1-[2-(diphenylmethoxy) ethyl]-4-(3-phenylpropyl)piperazine). In parkinsonian putamen, mazindol competitively inhibited the binding of [3H]GBR-12935 with an estimated affinity (Ki approximately 2,000 nM) 10 times lower than in controls (Ki approximately 30 nM), while the affinity of maxindol for [3H]GBR-12935 binding in the caudate was equal to that seen with controls (Ki approximately 50 nM). The proportion of [3H]GBR-12935 binding sites recognized by mazindol with high affinity in Parkinson's diseased caudate was, however, reduced by 50-80%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The dopamine transporter is absent in parkinsonian putamen and reduced in the caudate nucleus. 198 18

Dopamine receptors are classified into D1 and D2 subtypes on the basis of their pharmacological properties and the intracellular responses they mediate. The cerebral D2 dopamine receptor is the target of drugs used to alleviate the main symptoms of schizophrenia. Although it is considered to be a single molecular entity, there is evidence that multiple D2-receptor subtypes exist. A complementary DNA encoding a D2 receptor has recently been cloned and the deduced 415-amino-acid sequence indicates that it belongs to the large superfamily of receptors coupled to G proteins, and that its topology consists of seven transmembrane domains. In this family, the genes are frequently without introns and each is believed to encode a unique polypeptide product. Here we show that the gene for the D2 receptor produces two receptor isoforms by alternative messenger RNA splicing, providing a route to receptor diversity in this family. One isoform corresponds to the D2(415) receptor, but the second contains an additional sequence encoding a 29-amino-acid fragment, defining a novel D2(444) receptor isoform. Expression of the two isoforms is tissue-specific, and both are regulated by guanyl nucleotides. As the extra sequence is located within a putative cytoplasmic loop that binds to G proteins, the two isoforms might interact with different G proteins and thereby initiate distinct intracellular signals.
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PMID:Alternative splicing directs the expression of two D2 dopamine receptor isoforms. 253 47

Concentrations of vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK) and gastrin in the cerebrospinal fluid (CSF) was studied in patients with endogenous depression, non-endogenous depression, mania, schizophrenia and a control group. All patients were classified according to various diagnostic systems. In the group of non-endogenously depressed patients CSF-VIP levels (median 16 pmol/l) were found significantly lowered compared to controls (median = 32 pmol/l) and endogenous depression (26 pmol/l). Going through the non-endogenous group it appeared that the low CSF-VIP was due to a group of patients with a former diagnosis of endogenous depression or a present diagnosis of possible endogenous depression. Moreover, this group was clinically characterized by 'dysphoric/hysterical features', 'reversed diurnal variation' (i.e. worst in the evening), and 'lack of clearly circumscribed episode'. In many aspects this group seems similar to the atypical depressions described as monoamineoxidase responders. Concerning CSF-CCK and CSF-gastrin no significant differences between the examined groups were demonstrated.
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PMID:Neuropeptides in the cerebrospinal fluid (CSF) in psychiatric disorders. 393 76

The human brain contains several peptides with probable synaptic actions, some of which form complex neuronal networks in the limbic lobe (amygdala, hippocampus and temporal cortex). A limbic lobe abnormality has been postulated in schizophrenia on the basis of similarities between schizophrenic symptoms and symptoms in cases of known limbic pathology. Cholecystokinin (CCK), somatostatin (SRIF), neurotensin (NT), vasoactive intestinal polypeptide (VIP) and substance P (SP)-like immunoreactivities were measured by radioimmunoassay in 10 brain areas of 14 schizophrenics and 12 controls. In the schizophrenic group symptoms had been rated in life and the group was divided into Type I (n = 7) and Type II (n = 7) subgroups on the basis of the absence or presence of morbid negative symptoms. In control brains each peptide showed a characteristic distribution with high levels in cortex (CCK), limbic lobe (SOM, NT, VIP) or striatal areas (SP) and low levels of each of the peptides in thalamus. Significant (P less than 0.05) differences between groups were: reductions of CCK and SOM in hippocampus and CCK in amygdala in Type II schizophrenics, and CCK in the temporal cortex of the total schizophrenic group; and elevations of VIP in amygdala in Type I schizophrenics and of SP in the hippocampus in the total schizophrenic group. The findings could not be explained by variables such as age, delay between death and necropsy or to neuroleptic medication. These clinical-state related alterations in the peptide content of the limbic system in schizophrenia may illuminate the pathophysiological basis of the disease, particularly the distinction between Type I and II syndromes.
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PMID:Peptides, the limbic lobe and schizophrenia. 619 24

Neurotensin (NT) has been proposed to be an endogenous neuroleptic based on observations that i.c.v. administration of this peptide antagonizes dopamine-mediated behavior. Because NT influences dopamine activity, this peptide may contribute to the pathogenesis of psychotic disorders such as schizophrenia; however, the precise physiological effects of NT remain speculative. In order to elucidate the function of endogenous NT, a selective NT antiserum (NTAS) was administered i.c.v. through a push-pull cannula in unanesthetized, freely moving rats in combination with dopamine activation caused by methamphetamine (METH). Locomotor and rearing activities induced by a low dose of METH (0.5 mg/kg) were substantially enhanced (4-5-fold) in rats receiving NTAS compared to control animals receiving METH alone. Similarly raised antiserum to vasoactive intestinal polypeptide (VIP) did not alter METH-induced effects. To determine a possible mechanism for these observations, perfusate delivered into the cerebral ventricular space was collected by push-pull cannulae and assayed for dopamine release. METH-induced dopamine release was enhanced 4-5-fold by co-administration of NTAS but not VIP antiserum. To verify these observations, and to identify the site of dopamine release, this experiment was repeated utilizing microdialysis and the recently described NT antagonist, SR-48692. Results from this experiment were similar to those found using NTAS. Like NTAS, co-administration of the NT antagonist enhanced the behavioral responses to a low dose of METH. These studies with SR-48692 also revealed that blockade of NT receptors increased METH-induced release of dopamine from the nucleus accumbens. These findings are the first to demonstrate directly that endogenous NT antagonizes stimulated dopamine pathways and its inactivation substantially enhances METH-induced DA release and related behaviors.
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PMID:Endogenous neurotensin antagonizes methamphetamine-enhanced dopaminergic activity. 789 59

sigma Receptors have been implicated in many pharmacological and physiological functions. sigma Receptors were purported to modulate behavioral alteration induced by cocaine and amphetamine, mediate effects of certain atypical antipsychotic agents, affect tonic potassium channels, the PCP/NMDA receptor complex, duodenal bicarbonate secretion, and CRF-induced colonic motility. sigma Receptors were reported to be altered in schizophrenia in certain studies, and up- and downregulations of sigma receptors have been observed in certain conditions. Neuropeptide Y has been shown to modulate the PCP/NMDA receptor complex in both central and gastrointestinal systems via sigma receptors. sigma Receptors are G-protein linked, and certain actions of sigma receptor ligands were affected by G-protein-modifying agents. Using photoaffinity labeling technique, a polypeptide of about 26 kDa has been identified as a sigma receptor. However, the exact biochemical relationship of this polypeptide to sigma receptors is unknown at present.
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PMID:Delineating biochemical and functional properties of sigma receptors: emerging concepts. 810 75

Neuropeptide concentrations were determined in the postmortem cerebral cortex from 19 cognitive-impaired schizophrenics, 4 normal elderly subjects, 4 multi-infarct dementia (MID) cases, and 13 Alzheimer's disease (AD) patients. Only AD patients met criteria for AD. The normal elderly and MID cases were combined into one control group. Somatostatin concentrations were reduced in both schizophrenia and AD. Neuropeptide Y concentrations were reduced only in schizophrenia, and corticotropin-releasing hormone concentrations were primarily reduced in AD. Concentrations of vasoactive intestinal polypeptide and cholecystokinin also were reduced in schizophrenia, although not as profoundly as somatostatin or neuropeptide Y. In AD, cholecystokinin and vasoactive intestinal peptide were unchanged. Neuropeptide deficits in schizophrenics were more pronounced in the temporal and frontal lobes than in the occipital lobe. The mechanisms underlying these deficits in schizophrenia and AD are likely distinct. In schizophrenia, a common neural element, perhaps the cerebral cortical gaba-aminobutyric acid (GABA)-containing neuron, may underlie these deficits.
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PMID:Neuropeptide deficits in schizophrenia vs. Alzheimer's disease cerebral cortex. 871 4

Monozygotic twins discordant for schizophrenia were analyzed by two-dimensional (2-D) gel electrophoresis to identify extrahereditary factors important in the development of schizophrenia. Plasma protein patterns in 2-D gels of monozygotic twins discordant for schizophrenia were found to be significantly less alike than those of normal control monozygotic twins. Several polypeptide spots were found to be elevated in the plasma of the schizophrenic twin. One of these polypeptides, spot 782, was also found to be significantly (p < .001) elevated when schizophrenic patients were compared to unrelated normal control individuals. Spot 782 may be an isoform of haptoglobin. Quantitative variations in some plasma haptoglobin levels were seen between discordant twins, but not between unrelated schizophrenic and normal control individuals.
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PMID:Plasma protein variations in monozygotic twins discordant for schizophrenia. 887 62


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