Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle or of a sham lesion on the neuropeptide content of the striatum and substantia nigra was investigated with or without 6 months L-3,4-dihydroxyphenylalanine (L-DOPA; 200 mg/kg per day) plus carbidopa (25 mg/kg per day) treatment. [Met5]- and [Leu5]enkephalin, substance P (SP), neurotensin (NT) and cholecystokinin (CCK) were measured by a combined HPLC/RIA method. Neurotensin levels were increased in the striatum, and [Leu5]enkephalin, and SP levels were reduced in the substantia nigra as a consequence of the lesion, while the levels of other peptides were unaltered. Administration of L-DOPA to sham-operated rats bilaterally increased SP levels in striatum and substantia nigra, and [Met5]enkephalin and CCK content in substantia nigra. L-DOPA treatment of 6-OHDA-lesioned rats increased [Met5]- and [Leu5]enkephalin and CCK levels in the striatum ipsilateral to the lesion but not on the intact side. In the substantia nigra, the lesion-induced decrease in [Leu5]enkephalin and SP was reversed by L-DOPA treatment, [Met5]enkephalin and CCK levels ipsilateral to the lesion were further enhanced, and there was an increase in NT ipsilateral to the lesion. Cryptic [Met5]- and [Leu5]enkephalin increased in the ipsilateral striatum following an 6-OHDA lesion. L-DOPA treatment did not alter cryptic enkephalin levels or the lesion-induced increase in cryptic [Met5]enkephalin, while cryptic [Leu5]enkephalin was further increased in lesioned animals given L-DOPA. These results suggest that the pattern of change in basal ganglia peptides in Parkinson's disease is not due solely to the destruction of the nigrostriatal pathway, the drug treatment of the disease or a combination of these factors.
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PMID:Effects of a unilateral 6-hydroxydopamine lesion and prolonged L-3,4-dihydroxyphenylalanine treatment on peptidergic systems in rat basal ganglia. 138 71

Aged common marmosets were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 0.5-2.0 mg/kg/week i.p.) for 16 or 24 weeks, observed for a total of 30 weeks and then killed for measurement of biochemical parameters in basal ganglia. The MPTP treatment induced a marked depletion in dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels in the caudate nucleus and putamen. In contrast, the concentrations of five neuropeptides: [Met5]-enkephalin, [Leu5]-enkephalin, cholecystokinin, substance P and neurotensin as measured by a combined HPLC/RIA method, remained unaltered in all basal ganglia regions examined. Enkephalin precursor levels, as reflected by cryptic [Met5]-enkephalin content, were increased in the putamen, but not in the caudate nucleus, as a consequence of MPTP administration. Cryptic [Leu5]-enkephalin content remained unchanged in the striatum of MPTP treated marmosets. Overall, these results suggest an increase in striatal [Met5]-enkephalin release following chronic MPTP treatment of aged marmosets. However, the chronic treatment of aged marmosets with MPTP does not reproduce the neuropeptide alterations characteristic of Parkinson's disease.
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PMID:Neuropeptide levels in the basal ganglia of aged common marmosets following prolonged treatment with MPTP. 171 7

The aim of the present study was to examine the effects of neurotensin in an animal model of Parkinson's disease (PD). Bilateral administration of 6-OHDA in the medial forebrain bundle at the level of the posterolateral hypothalamus of rats resulted in the appearance of the 3 principal neurological signs of PD: hypokinesia, rigidity and tremor. These symptoms were accompanied by severe losses of dopamine and its main metabolites in terminal regions of well-known dopamine pathways. Norepinephrine concentrations were also decreased in several regions but to a lesser extent than dopamine. Intracerebroventricular administration of neurotensin, in doses ranging from 7.5 to 120.0 micrograms, resulted in dose related attenuations of both muscular rigidity and tremors of animals. However, hypokinesia, defined as decreased motor activity was not significantly affected by the peptide. Administration of 120.0 micrograms of [Ala]NT, an inactive analogue of neurotensin, failed to alter any of the 3 neurological signs. Together, these results reveal selective antiparkinson-like effects of neurotensin in an animal model. The theoretical significance of these findings is discussed.
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PMID:Antiparkinson-like effects of neurotensin in 6-hydroxydopamine lesioned rats. 190 4

The technique of receptor autoradiography was used to study the distribution of neurotensin receptors in post mortem brain tissues from patients affected by Parkinson's disease, progressive supranuclear palsy and from age-matched controls. [125I]Neurotensin was used as ligand. Significant receptor decreases were found in the substantia nigra, both pars compacta and reticulata, and in the putamen in Parkinson's disease and progressive supranuclear palsy. In addition, significant decreases of neurotensin receptors were found in the ventral tegmental area, nucleus accumbens and dorsal part of caudate head in patients with Parkinson's disease but not in patients with progressive supranuclear palsy, indicating differential involvement of neurotensin receptors in these two neurological disorders. In addition, both in Parkinson's disease and progressive supranuclear palsy the decrement of striatal neurotensin binding sites was less than expected from the reported decrease of dopamine content in this nucleus, suggesting only partial localization of neurotensin receptors on mesostriatal dopaminergic projections.
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PMID:Neurotensin receptors in Parkinson's disease and progressive supranuclear palsy: an autoradiographic study in basal ganglia. 196 15

Thirty years ago, dopamine was identified as an essential neurotransmittor. Since then, it has been the most written about CNS molecule. Considerable evidence implicates disturbances of brain dopamine function in the pathophysiology of several psychiatric and neurologic disorders, especially schizophrenia and Parkinson's disease. In the last decade, there have been important advances in the understanding of the diversity of CNS dopamine neurons and the chemical basis of this diversity, which relies upon molecular physiology of D1 and D2 receptors. Heterogeneity is remarkable at different levels, anatomical, biochemical, morphological or functional; besides, region specific interactions with other neurotransmittors and sometimes colocalisation of dopamine with cholecystokinin and/or neurotensin suggest the integration of dopamine neurons in functional subunits.
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PMID:[The mesencephalic dopaminergic system. Implications for neuroleptic treatment]. 197 42

The study of neurotransmitter receptors aids in the understanding of the normal anatomy, pharmacology, therapeutics and pathophysiology of disease processes involving the basal ganglia. Receptors may be studied in vitro by homogenate binding experiments, enzyme analysis or quantitative autoradiography and in vivo with positron emission tomography. In the substantia nigra (SN), receptors have been identified for somatostatin, neurotensin, substance P, glycine, benzodiazepine and GABA, opiates, dopamine, angiotensin converting enzyme (ACE) and serotonin. The striatum has receptors for dopamine, GABA and benzodiazepines, acetylcholine, opiates, substance P, glutamate and cholecystokinin. GABA and benzodiazepine receptors are also located in the globus pallidus. In Parkinson's disease, striatal dopamine D-2 receptors are elevated in patients that have not received L-DOPA therapy. This supersensitivity is reversed with agonist therapy. Muscarinic binding to cholinergic receptors seems to correlate with dopamine receptors. Delta opiate receptors are increased in the caudate and mu binding is reduced in the striatum. In the SN of patients with Parkinson's disease, there is reduced binding of somatostatin, neurotensin, mu and kappa opiates, benzodiazepine and GABA and glycine. In Huntington's disease, there is reduced binding of GABA and benzodiazepines, dopamine, acetylcholine, glutamate and CCK. There is increased binding of GABA in both the SN and globus pallidus. Glycine binding is increased in the substantia nigra and ACE is reduced.
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PMID:Receptors in the basal ganglia. 282 9

The regional distribution of neurotensin-like immunoreactivity was investigated in normal human brain and in brains of patients who had died with neurological illness. In Huntington's disease, neurotensin was increased in the pallidum, whilst in Parkinson's disease no significant changes in neurotensin content were observed. Similarly no changes were found in the telencephalic neurotensin content in senile dementia of the Alzheimer type. High levels of neurotensin-like immunoreactivity were detected in lumbar cerebrospinal fluid from patients and the characterization of the immunoreactive material by high-performance liquid chromatography showed it to be indistinguishable from synthetic neurotensin.
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PMID:Neurotensin in human brain: regional distribution and effects of neurological illness. 293 23

In the past twenty years, more than thirty peptides have been discovered to be present in the mammalian central nervous system (CNS). As the neuroanatomical distribution, neurochemical, electrophysiological and pharmacobehavioral effects of this novel group of neuroregulators have been described, it is evident that certain of these peptide-containing neural circuits may be pathologically altered in neuropsychiatric disorders. Although much attention has been focused on the opioid peptides, substantial data strongly support the hypothesis that non-opioid peptides such as somatostatin, neurotensin and substance P are altered in a diverse number of neuropsychiatric disorders including Alzheimer's disease, Huntington's chorea, Parkinson's disease, major depression and schizophrenia.
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PMID:Involvement of non-opioid peptides in the pathogenesis of neurological and psychiatric disorders: evidence from CSF and post-mortem studies. 293 45

Autoradiographic studies reveal densities of binding to somatostatin, neurotensin, mu-opiate, and benzodiazepine receptors in substantia nigra specimens from neurologically normal human brains. Binding to nigral angiotensin converting enzyme is also dense, whereas more modest densities of kappa-opiate, dopamine, and serotonin receptors are noted. In nigral specimens taken from patients with idiopathic Parkinson's disease, substantial reductions in somatostatin, neurotensin, mu-opiate and kappa-opiate receptors contrast with more modest reductions in dopamine and benzodiazepine I receptor subtypes. Angiotensin converting enzyme, serotonin, and benzodiazepine II binding are virtually unaltered. These results underscore the likelihood of strong peptidergic influences on normal and pathologically altered human nigrostriatal circuitry.
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PMID:Parkinson's disease: nigral receptor changes support peptidergic role in nigrostriatal modulation. 301 28

Frozen samples of postmortem human brain tissue from patients with Parkinson's disease (n = 25) and control patients who died without neurological disease (n = 25) were assayed for neurotensin and bombesin by specific radioimmunoassay. Twelve brain regions were examined: substantia nigra, ventral tegmental area, periaqueductal gray matter, caudate nucleus, putamen, globus pallidus, amygdala, hippocampus, nucleus accumbens, frontal cortex, cingulate cortex, and entorhinal cortex. In patients with Parkinson's disease, the concentration of bombesin was significantly decreased in the caudate nucleus and globus pallidus, and the concentration of neurotensin was significantly reduced in the hippocampus. The concentration of neither peptide was significantly altered in the substantia nigra or ventral tegmental area, two regions known to exhibit reductions in other neurotransmitter substances.
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PMID:Alterations in regional brain concentrations of neurotensin and bombesin in Parkinson's disease. 400 52


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