Alterations in regional brain concentrations of neurotensin and bombesin in Parkinson's disease

Bissette, Garth; Nemeroff, Charles B.; Decker, Michael; Kizer, John S.; Agid, Yves

doi:10.1002/ana.410170403

Cited by 62 publications

(15 citation statements)

References 22 publications

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“…Although an increase in striatal NT concentration was reported following a unilateral 6-hydroxydopamine lesion of rats (Engber et al, 1992;Masuo et al, 1990;Taylor et al, 1992), in MPTP-lesioned monkeys, NT levels in the caudate nucleus and putamen remained unaltered (Taylor et al, 1991). Furthermore, the NT content in the caudate and putamen was reported to be unchanged in Parkinson's disease patients (Bissette et al, 1985;Fernandez et al, 1995). In contrast, there was an increase in NT in the substantia nigra in Parkinson's disease patients compared to healthy controls (Fernandez et al, 1995(Fernandez et al, , 1996.…”

Section: Introductionmentioning

confidence: 48%

“…Similarly, the decrement of NT binding sites was found to be less than the decrease of DA content in the striatum of postmortem brain tissues from patients affected by Parkinson's disease (Chinaglia et al, 1990;Fernandez et al, 1994). Furthermore, NT levels have been found to be normal in the caudateputamen in parkinsonism (Bissette et al, 1985;Fernandez et al, 1995;Taylor et al, 1991) in spite of loss of nigral dopaminergic neurons (Kish et al, 1988;Parent and Lavoie, 1993). Hence, the above observations suggest only partial localization of NT receptors on nigrostriatal DAergic projections.…”

Section: Discussionmentioning

confidence: 88%

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Neurotensin receptors and dopamine transporters: Effects of MPTP lesioning and chronic dopaminergic treatments in monkeys

Goulet

Morissette

Grondin

et al. 1999

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The effect of denervation with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) of the dopamine (DA) nigrostriatal pathway on neurotensin (NT) receptor and DA transporter (DAT) in basal ganglia of monkeys (Macaca fascicularis) was investigated. The MPTP lesion induced a marked depletion of DA (90% or more vs. control) in the caudate nucleus and putamen. The densities of NT agonist binding sites labeled with [125I]NT and the NT antagonist binding sites labeled with [3H]SR142948A decreased by half in the caudate-putamen of MPTP-monkeys. In addition, the densities of [125I]NT and [3H]SR142948A binding sites markedly decreased (-77 and -63%, respectively) in the substantia nigra of MPTP-monkeys. Levocabastine did not compete with high affinity for [125I]NT binding in the monkey cingulate cortex, suggesting that only one class of NT receptors was labelled in the monkey brain. An extensive decrease of [3H]GBR12935 DAT binding sites (-92% vs. Control) was observed in the striatum of MPTP-monkeys and an important loss of DAT mRNA(-86% vs. Control) was observed in substantia nigra. Treatments for 1 month with either the D1 agonist SKF-82958 (3 mg/kg/day) or the D2 agonist cabergoline (0.25 mg/kg/day) had no effect on the lesion-induced decrease in NT and DAT binding sites or DAT mRNA levels. The decrease of striatal NT binding sites was less than expected from the decrease of DA content in this nucleus, suggesting only partial localization of NT receptors on nigrostriatal DAergic projections. These data also suggest that under severe DA denervation, treatment with D1 or D2 DA agonists does not modulate NT receptors and DAT density.

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Section: Introductionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 88%

Neurotensin receptors and dopamine transporters: Effects of MPTP lesioning and chronic dopaminergic treatments in monkeys

Goulet

Morissette

Grondin

et al. 1999

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“…[149][150][151] Relationships between these neuromodulators and dementia were rarely investigated, but dementia severity was found to correlate with neurotensin concentration in the putamen.149…”

Section: Acetylcholinementioning

confidence: 98%

Intellectual Impairment in Parkinson's Disease: Clinical, Pathologic, and Biochemical Correlates

Cummings

1988

J Geriatr Psychiatry Neurol

200

104

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The prevalence of overt dementia in 27 studies representing 4,336 Parkinson's disease (PD) patients was 39.9%. The studies reporting the highest incidence of intellectual impairment (69.9%) used psychologic assessment techniques, whereas studies identifying the lowest prevalence of dementia (30.2%) depended on nonstandardized clinical examinations. Neuropsychologic investigations reveal that PD patients manifest impairment in memory, visuospatial skills, and set aptitude. Language function is largely spared. Intellectual deterioration in PD correlates with age, akinesia, duration, and treatment status. Neuropathologic and neurochemical observations demonstrate that PD is a heterogeneous disorder: the classic subcortical pathology with dopamine deficiency may be complicated by atrophy of nucleus basalis and superimposed cortical cholinergic deficits, and a few patients have the histopathologic hallmarks of Alzheimer's disease. Mild intellectual loss occurs with the classic pathology, and the more severe dementia syndromes have cholinergic alterations or Alzheimer's disease. Thus, PD includes several syndromes of intellectual impairment with variable pathologic and neurochemical correlates.

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“…Initial studies at the cellular level linked NT with the production of cGMP (6), phosphatidylinositol (PI) turnover (7), calcium mobilization (8), and the production of cAMP (9). Neurotensin has been found to be altered in several neuropsychiatric diseases, such as schizophrenia (10), Parkinson's disease (11), and Alzheimer's disease (12).…”

Section: Neurotensin (Nt)mentioning

confidence: 99%

Chimeric Rat/Human Neurotensin Receptors Localize a Region of the Receptor Sensitive to Binding of a Novel, Species-specific, Picomolar Affinity Peptide

Cusack

Groshan

McCormick

et al. 1996

Journal of Biological Chemistry

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and the ¶Mayo Protein Core Facility, Mayo Clinic, Rochester, Minnesota 55595 Recently, we reported the development of a speciesspecific neurotensin analog that displays selective binding affinity at the rat and human neurotensin (NT) receptor, L-[3,2-Nal 11 ]NT(8 -13) (where Nal is naphthylalanine) (NT19). We have developed another neurotensin analog, L-[3,1-Nal 11 ]NT(8 -13), (NT34), that exhibits a 126-fold difference in binding affinities between the rat and human receptors. This compound differs from our previous reported species-specific ligand in the steric positioning of the naphthyl ring on the L-alanine side chain. For NT34, the observed K d values at the rat and human neurotensin receptors were 0.046 and 5.8 nM, respectively. In stimulating phosphatidylinositol turnover, the observed EC 50 values were 2.8 nM and 130 nM in rat and human, respectively. We constructed a series of chimeric rat/human neurotensin receptor genes and expressed them by transient transfection into human embryonic kidney (HEK-293) cells. Radioligand binding assays were then performed using neurotensin and NT34. Our results led us to propose a region of the neurotensin receptor that may be involved in determining species specificity, i.e. the transmembrane VI, the third extracellular loop, and transmembrane VII regions of the neurotensin receptor. Neurotensin (NT)1 is a tridecapeptide that was originally isolated from the bovine hypothalamus (1). Since its discovery, NT has been found to be important in the mammalian central nervous system with effects that include hypothermia (2), antinociception (3), sedation and muscle relaxation (4), and decreased locomotor activity (5). Initial studies at the cellular level linked NT with the production of cGMP (6), phosphatidylinositol (PI) turnover (7), calcium mobilization (8), and the production of cAMP (9). Neurotensin has been found to be altered in several neuropsychiatric diseases, such as schizophrenia (10), Parkinson's disease (11), and Alzheimer's disease (12).Early work with NT showed that only the last six amino acids, namely NT(8 -13), are needed for receptor function (13). Our work has focused on developing novel NT analogs of NT(8 -13), both nonpeptide (14) as well as peptide forms (15). Recently, we reported the development of many new NT(8 -13) analogs, including a species-specific one, NT19, with a ␤-naphthylalanine substituted for tyrosine in position 11 of the native NT(8 -13). This compound displays much higher binding affinity at the rat NT receptor (NTR) compared to the binding at the human NTR (see above). At the molecular level, there are several differences between the rat (16) and human (17, 18) neurotensin receptors in their primary sequences. The rat receptor comprises 424 amino acids, while the human receptor consists of 6 fewer amino acids. In addition, the proteins share an 84% homology at the amino acid level, and both proteins display a transmembrane topology similar to that of other G-protein coupled receptors. Thus, the original placement of the NTR pro...

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Alterations in regional brain concentrations of neurotensin and bombesin in Parkinson's disease

Cited by 62 publications

References 22 publications

Neurotensin receptors and dopamine transporters: Effects of MPTP lesioning and chronic dopaminergic treatments in monkeys

Neurotensin receptors and dopamine transporters: Effects of MPTP lesioning and chronic dopaminergic treatments in monkeys

Intellectual Impairment in Parkinson's Disease: Clinical, Pathologic, and Biochemical Correlates

Chimeric Rat/Human Neurotensin Receptors Localize a Region of the Receptor Sensitive to Binding of a Novel, Species-specific, Picomolar Affinity Peptide

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