The Neurobiology of Neurotensin

Elliott, Peter J.; Nemeroff, Charles B.

doi:10.1007/978-1-4684-5152-8_17

Cited by 3 publications

(4 citation statements)

References 192 publications

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“…Neurotensin acts as a neuromodulator in the brain (5) and, in particular, as a modulator of dopamine transmission in the nigrostriatal and mesocorticolimbic systems (6,7). It has neuroendocrine actions such as the mediation of the preovulatory surge (8,9).…”

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confidence: 99%

Biochemical and pharmacological profile of a potent and selective nonpeptide antagonist of the neurotensin receptor.

Gully

Canton²,

Boigegrain³

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

373

251

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We describe the characteristics of SR 48692, a selective, nonpeptide antagonist of the neurotensin receptor. In vitro, this compound competitively inhibits 125I-labeled devoid of any intrinsic agonist activity. This compound is also active in vivo, since it reverses at low dose (80 pg/kg) the turning behavior induced by intrastriatal injection of neurotensin in mice with similar potency whatever the route of administration (i.p. or orally) and with a long duration of action (6 hr). Thus, being a potent and selective neurotensin receptor antagonist, SR 48692 may be considered as a powerful tool for investigating the role of neurotensin in physiological and pathological processes.

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confidence: 99%

Biochemical and pharmacological profile of a potent and selective nonpeptide antagonist of the neurotensin receptor.

Gully

Canton²,

Boigegrain³

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

373

251

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“…Neurotensin (NT), a tridecapeptide with widespread distribution in the central nervous system and peripheral tissues of mammals, is one of a family of structurally related peptides with members manifesting diverse biological activities (1). The structure of the rat gene encoding NT has recently been determined (2), and the general features of the predicted NT precursor for the rat are the same as those of the predicted precursors for the dog (3) and cow (2).…”

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“…There is increasing evidence that NT functions as a neuroregulatory substance in the mammalian central nervous system (1,5). Effects produced by NT administration in the central nervous system include hypothermia, hypotension, and antinociception.…”

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confidence: 99%

Distribution of neurotensin/neuromedin N mRNA in rat forebrain: unexpected abundance in hippocampus and subiculum.

Alexander

Miller

Dorsa

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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We have used in situ hybridization to determine the regional distribution of mRNA encoding the neurotensin/neuromedin N (NT/N) precursor in the forebrain of the adult male rat. Cells containing NT/N mRNA are widely distributed in the forebrain. These areas include the septum, bed nucleus of the stria terminalis, preoptic area, hypothalamus, amygdala, accumbens nucleus, caudate-putamen, and piriform and retrosplenial cortex. In general, the regional distribution of NT/N mRNA corresponds to the previously determined distribution of neurotensin-immunoreactive cell bodies; however, several notable exceptions were observed.The most striking difference occurs specifically in the CA1 region of the hippocampus, where intense labeling is associated with the pyramidal cell layer despite the reported absence of neurotensin-immunoreactive cells in this region. Analysis of microdissected tissue by S1 nuclease protection assay confirmed the abundance of authentic NT/N mRNA in CAL. A second major discrepancy between NT/N mRNA abundance and neurotensin-immunoreactivity occurs in the intensely labeled subiculum, a region that contains only scattered neurotensin-immunoreactive cells in the adult. These results suggest that, in specific regions of the forebrain, NT/N precursor is processed to yield products other than neurotensin. In addition, these results provide an anatomical basis for studying the physiological regulation of NT/N mRNA levels in the forebrain.Neurotensin (NT), a tridecapeptide with widespread distribution in the central nervous system and peripheral tissues of mammals, is one of a family of structurally related peptides with members manifesting diverse biological activities (1). The structure of the rat gene encoding NT has recently been determined (2), and the general features of the predicted NT precursor for the rat are the same as those of the predicted precursors for the dog (3) and cow (2). In each species, a precursor protein of 169-170 amino acid residues encodes both NT and neuromedin N, a peptide similar in structure to NT (4). A comparison of the sequences of the complete neurotensin/neuromedin N (NT/N) precursor from rat, dog, and cow reveals a high degree of conservation. This finding is consistent with the idea that the precursor may be processed to yield biologically active peptides that are as yet unknown.There is increasing evidence that NT functions as a neuroregulatory substance in the mammalian central nervous system (1, 5). Effects produced by NT administration in the central nervous system include hypothermia, hypotension, and antinociception. NT has also been implicated in the central regulation of anterior pituitary function (6, 7). NTimmunoreactive cell bodies are most numerous in the forebrain, with widespread distribution in limbic regions such as the septum, preoptic area, hypothalamus, and amygdala (8).Other forebrain regions, such as the dorsal subiculum, contain many NT-immunoreactive cell bodies during early stages of development, but the number of neurons with detectable...

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“…Neurotensin (NT) is a tridecapeptide that has been documented to play a neuromodulatory role in both central and peripheral nervous systems (see Elliott and Nemeroff, 1987;Nemeroff et al, 1980, for reviews). These modulatory effects are exerted through activation of G-protein-linked high affinity receptors (& = 0.3-0.4 nM) (Kitabgi et al, 1977;Uhl et al, 1977; for a review, see Kitabgi et al, 1985).…”

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confidence: 99%

Binding and internalization of neurotensin in hybrid cells derived from septa1 cholinergic neurons

Faure

Labbé-Jullié

Cashman

et al. 1995

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Autoradiographic studies from our laboratory have previously demonstrated a selective association of high affinity neurotensin (NT) binding sites with basal forebrain cholinergic neurons. In search of an in vitro model for further characterization of the role and regulation of these sites, we have examined the binding and internalization of 125I-Tyr3-NT (125I-NT) and fluorescein isothiocyanate (FITC)-conjugated NT (fluo-NT) on SN17 hybrid cells, produced by fusion of embryonic murine septal cells with neuroblastoma. 125I-NT binding to SN17 membrane preparations was specific and saturable. Scatchard analysis of the data was suggestive of an interaction with a single population of sites, the affinity (Kd = 1.7 nM) and pharmacological profile of which were comparable to those of neural NT receptors. No specific binding was observed on the parent neuroblastoma cell line, confirming that the expression of those sites is a neuronal trait. Incubation of whole SN17 cells with 125I-NT resulted in a time- and temperature-dependent internalization of the specifically bound peptide. The t1/2 of this internalization was estimated at 13 min, a value nearly identical to that reported for neurons in culture. Confocal microscopic analyses using fluo-NT indicated that the internalization process was endocytic in nature in that: 1) it was entirely blocked by the endocytosis inhibitor phenylarsine oxide; and 2) it was mediated through small intracytoplasmic particles the size and maturation of which corresponded to that of endosomes. It is proposed that the expression and internalization of NT receptors by SN17 hybrid cells represent a new facet of these cells' cholinergic phenotype that makes them amenable to the study of NT interactions with cholinergic cells.

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The Neurobiology of Neurotensin

Cited by 3 publications

References 192 publications

Biochemical and pharmacological profile of a potent and selective nonpeptide antagonist of the neurotensin receptor.

Biochemical and pharmacological profile of a potent and selective nonpeptide antagonist of the neurotensin receptor.

Distribution of neurotensin/neuromedin N mRNA in rat forebrain: unexpected abundance in hippocampus and subiculum.

Binding and internalization of neurotensin in hybrid cells derived from septa1 cholinergic neurons

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