Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of common marmosets with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 1-4 mg/kg for up to 4 days) caused a profound parkinsonian state. Ten days from the start of MPTP treatment, all animals showed marked motor impairment, consisting of bradykinesia and akinesia, limb rigidity, postural abnormalities, loss of vocalisation and blink reflex, and, on occasions, postural tremor. Measurement of caudate-putamen monoamine content at this time showed a profound loss in 3,4-dihydroxyphenylethylamine, homovanillic acid, and 3,4-dihydroxyphenylacetic acid concentrations. Measurement of neuropeptide concentrations in the caudate-putamen, internal and external segments of the globus pallidus, nucleus accumbens, substantia nigra, frontal cortex, and hippocampus showed met-enkephalin, leu-enkephalin, and cholecystokinin (CCK-8) concentrations to be unaffected by MPTP treatment. There was a small decrease in the substance P content of frontal cortex, but otherwise the content of this neuropeptide was unaltered. Parkinsonism in the marmoset, induced by MPTP treatment 10 days earlier, does not alter neuropeptide concentrations in the manner observed in Parkinson's disease.
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PMID:Lack of change in basal ganglia neuropeptide content following subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of the common marmoset. 242 37

Fluphenazine decanoate (25 mg/kg IM every 3 weeks x 6) resulted in spontaneous vacuous chewing mouth movements and jaw tremor in male Sprague-Dawley rats. These movements could be suppressed by the selective D1 or D2 dopamine antagonists SCH 23390 (0.5 mg/kg) and raclopride (0.5 mg/kg), respectively, and by CCK-8S (50 micrograms/kg). Fluphenazine-induced mouth movements were unaffected by the selective CCK antagonist MK-329, and by a dose of physostigmine (50 micrograms/kg) sufficient to stimulate mouth movements in placebo treated rats. Scopolamine (0.1 mg/kg) suppressed spontaneous mouth movements in placebo-treated rats, but the effect on fluphenazine-induced mouth movements was not significant. A higher dose of scopolamine (0.5 mg/kg) did suppress the neuroleptic-induced mouth movements, but also induced hyperactivity, characterized by increased sniffing and grooming. These findings indicate that mouth movements resulting from the chronic administration of neuroleptics to the rat may serve as a useful pharmacological model of tardive dyskinesia in the human, and suggest that a relative increase of D1 activity as well as impaired CCK function may contribute to the pathogenesis of this disorder.
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PMID:Chronic neuroleptic-induced mouth movements in the rat: suppression by CCK and selective dopamine D1 and D2 receptor antagonists. 256 57

The anticonvulsive activity of cholecystokinin octapeptide sulphate ester (CCK-8-SE), non-sulphated cholecystokinin octapeptide (CCK-8-NS) and three different N- and C-terminal fragments were investigated against seizures induced by picrotoxin and electroshock in rats after intracerebroventricular administration. Doses of 0.8 and 80 pmol of CCK-8-SE and CCK-8-NS significantly enhanced the latency of seizures induced by picrotoxin and shortened the duration of the clonic phase of the seizures induced by electroshock. Only CCK-8-SE shortened the recovery time and only 0.8 pmol of CCK-8-SE could shorten the duration of the tonic phase of convulsions induced by electroshock. Doses of the octapeptides of 8000 pmol were ineffective, with the exception of CCK-8-NS in the picrotoxin test. Of the fragments tested, the C-terminal tetrapeptide, CCK-5-8, enhanced the latency of seizures induced by picrotoxin in a dose of 0.8 pmol, and had a dose-dependent biphasic effect on the duration of the clonic phase of seizures induced by electroshock. Intracerebroventricular administration of diazepam enhanced only the latency of tremor and clonic seizures induced with picrotoxin in a dose of 40 nmol. Twelve nmole of diazepam shortened the clonic phase of convulsions induced by electroshock. The peptides tested were much more active than diazepam, and their effective doses were comparable to the amounts of cholecystokinin octapeptide found in brain structures.
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PMID:Inhibition of seizures induced by picrotoxin and electroshock by cholecystokinin octapeptides and their fragments in rats after intracerebroventricular administration. 609 Sep 68

Intracerebroventricular (i.c.v.) injection of C-terminal octapeptide of cholecystokinin (CCK-8) in rats prolonged pentobarbital- and ethanol-induced sleeping time, but non-sulfated CCD-8 (CCK-8-NS) had no effect and caerulein showed a tendency to prolong the pentobarbital narcosis. On the other hand, i.c.v. injection of thyrotropin releasing hormone (TRH) shortened the sleeping time and the effect of CCK-8 was apparently antagonized by combined administration of TRH. Spontaneous locomotor activity in the late morning and early afternoon was not affected by CCK-8, but it increased following i.c.v. injection of CCK-8-NS. Hyperactivity produced by TRH and methamphetamine was suppressed by i.c.v. injection of CCK-8, while CCK-8-NS showed a tendency to enhance the methamphetamine-induced hyperactivity and caerulein had no effect. These results indicate that CCK-8 has a sedative action and antagonizes the behavioral excitation caused by TRH and methamphetamine, but that the effects of CCK-8-NS and caerulein were rather the opposite of those of CCK-8. In an additional experiment the TRH-induced body shaking response was not affected by combined administration of CCK-8.
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PMID:Sedative action of cholecystokinin octapeptide on behavioral excitation by thyrotropin releasing hormone and methamphetamine in the rat. 628 7

Effects of intracerebroventricular administration of beta-endorphin, thyrotropin-releasing hormone (TRH), cholecystokinin octapeptide (CCK-8), non-sulfated CCK-8 (CCK-8-NS) and caerulein on body shaking behavior were observed in rats. CCK-8 and its related peptides produced only a small increase in the number of body shakes, while TRH had the striking effect of stimulating body shakes, this increase being markedly suppressed by simultaneous administration of beta-endorphin. Moreover, the suppressive effect of beta-endorphin on TRH-induced body shakes was antagonized by simultaneous administration of caerulein and CCK-8. The body shakes induced by ice-water immersion were also reduced by beta-endorphin, this beta-endorphin effect being partly antagonized by caerulein and CCK-8.
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PMID:Effects of beta-endorphin, thyrotropin-releasing hormone and cholecystokinin on body shaking behavior in rats. 629 91

Parkinson's disease (PD) is a progressive neurodegenerative disease affecting the ventral midbrain dopaminergic neurons, resulting in motor defects mainly tremor, rigidity, and bradykinesia along with a wide array of non-motor symptoms. The current study is focused on determining the potential druggable targets of PD by consolidating gene expression profiling and network methodology. Initially, the differentially expressed genes were established from which the central network was constructed by assimilating the interacting partners. Investigating the topological parameters of the network, the genes SYT1, CXCR4, CDC42, KIT, RET, DRD2, NTN1, PRKACB, KDR, NR4A2, SLC18A2, CCK, TH, KCNJ6, and TAC1 were identified as the hub genes and can be explored as potential candidate genes for PD therapeutics. Gene ontology and cluster analysis of the hub genes has provided further insights about the pathophysiology of the disease. Among the hub genes, PRKACB is observed in relatively all the enriched pathways which are modulated by G protein-coupled receptors through protein kinases. Further, we noticed SYT1 as a novel biomarker for PD. Moreover, the regulatory network was constructed with the hub genes as seed nodes with associated transcription factors (TFs) and microRNA (miRNAs). In this analysis, we identified MYC as the major TF and the miRNAs miR-21, miR-155, miR-7, and miR26A1 have a significant role in modulating the hub genes. Briefly, these significant hub genes and their enriched pathways, TFs, and miRNAs have aided in the better understanding of molecular mechanisms underlying PD and its potential core target genes.
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PMID:Integrative Analysis of Gene Expression and Regulatory Network Interaction Data Reveals the Protein Kinase C Family of Serine/Threonine Receptors as a Significant Druggable Target for Parkinson's Disease. 3272 98