Rapid agonist-induced decrease of neurotensin receptors from the cell surface in rat cultured neurons

Vanisberg, Marie-Agnès; Maloteaux, Jean‐Marie; Octave, Jean‐Noël; Laduron, Pierre M.

doi:10.1016/0006-2952(91)90229-x

Cited by 44 publications

(21 citation statements)

References 31 publications

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“…In fact, biochemical studies have indicated that this internalization process was likely to subserve receptor down-regulation (54) or even transmembrane signaling ( 5 5). The particulate appearance of internalized fluorescent molecules observed in the present study strongly suggests that the internalization process is carried out through an endosomal compartment, as previously demonstrated in neurons for other non-transmitter molecules (56).…”

Section: Discussionmentioning

confidence: 99%

Synthesis of a biologically active fluorescent probe for labeling neurotensin receptors.

Faure¹,

Gaudreau²,

Shaw³

et al. 1994

J Histochem Cytochem.

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Section: Discussionmentioning

confidence: 99%

Synthesis of a biologically active fluorescent probe for labeling neurotensin receptors.

Faure¹,

Gaudreau²,

Shaw³

et al. 1994

J Histochem Cytochem.

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“…The finding that NT receptor upregulation occurs in the presence of increased levels of NT in the colonic mucosa is somewhat unexpected, because in vitro evidence indicates that agonist exposure induces loss of cell-surface receptors for NT (45). However, this finding is not without precedent.…”

Section: Figurementioning

confidence: 99%

Neurotensin is a proinflammatory neuropeptide in colonic inflammation

Castagliuolo¹,

Wang²,

Valenick³

et al. 1999

J. Clin. Invest.

130

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A growing body of evidence suggests that interaction of epithelial and immune cells via neuropeptides, hormones, and cytokines participate in the pathophysiology of diarrhea and intestinal inflammation (reviewed in ref. 1). Neurotensin (NT), a bioactive peptide (2) with a primary distribution in the brain and the gastrointestinal tract, has been localized by immunohistochemistry to endocrine cells (N cells) and neurons in the intestinal mucosa, submucosa, and muscularis of animals and humans (3). A wide range of biological activities has been described for NT with actions on the cardiovascular, gastrointestinal, reproductive, and central nervous systems (3). The known intestinal effects of this peptide include trophic effects on small and large bowel, pancreas, and stomach; inhibition of small bowel and gastric motility; and stimulation of colonic motor activity (3). Studies in animals (3, 4, 5) and humans (3, 6) also demonstrate that NT may modulate fluid secretion in the intestinal tract and that its secretory effects in the ileum may be mediated through a nervous reflex in the enteric nervous system (5).Several lines of evidence indicate that NT may also participate in inflammatory reactions. Intravenous administration of NT to rats causes mast cell degranulation (7) and increases vascular permeability and levels of histamine and leukotriene C4 in the plasma (8); these effects can be inhibited by a specific NT receptor antagonist (9).NT also interacts in vitro with immune and inflammatory cells, including leukocytes (10), peritoneal mast cells (7), and macrophages (11,12). Although these studies point to a role for NT in inflammatory reactions, the possibility that this peptide participates in the pathogenesis of colonic inflammation has not been examined.NT exerts its effects by interacting with specific receptors (NTR) on cell surfaces. Two specific receptors for NT (NTR1 and NTR2), which belong to the seven transmembrane G protein-linked superfamily, have been identified and cloned (13,14). NTR1-mRNA and NT binding sites have been identified in the brain (15), small and large intestine of animals and humans (13, 15), human colonic epithelial cell lines (16,17), human blood mononuclear cells (11), and endothelial cells (18). Recently, we demonstrated the presence of NTR1 mRNA in the rat colonic mucosa, including colonic epithelial cells (19). We also showed that administration of the specific NT receptor nonpeptide antagonist SR-48,692 to rats attenuated colonic mucin secretion and mast cell activation following immobilization stress, indicating a critical role for NT in stress-related colonic responses (19).Clostridium difficile is the primary pathogenic factor of antibiotic-associated diarrhea in humans and animals The neuropeptide neurotensin mediates several intestinal functions, including chloride secretion, motility, and cellular growth. However, whether this peptide participates in intestinal inflammation is not known. Toxin A, an enterotoxin from Clostridium difficile, mediates pseudomembranous col...

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“…NTR Gene Activation Requires Receptor Internalization-It is known that NT induces the internalization of NTR in a number of cell lines including HT-29 (12,14). Previous experiments have shown that in rat basal forebrain slices and in septal neuroblastoma cells (SN17), NT-NTR internalized complex is transported from the cell periphery to the perinuclear region by endosomes (34,35).…”

Section: Ntr Gene Activation Requires Protein Synthesis-mentioning

confidence: 99%

“…In the case of NT, several studies have shown that variations in NTR expression were caused by changes in NT levels. For example, acute agonist stimulation of NTR induces desensitization and down-regulation of receptor in primary cultures of rat forebrain and HT-29 cells (12,13). Prolonged exposure of N1E-115 cells to NT resulted in the disappearance of most NT-binding sites, and de novo synthesis of NTR was required for the recovery of receptor-binding sites and function (14).…”

mentioning

confidence: 99%

Neurotensin Agonist Induces Differential Regulation of Neurotensin Receptor mRNA

Souazé

Rostène

Forgez

1997

Journal of Biological Chemistry

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The binding of neurotensin (NT) to specific receptors triggers the multiple functions that NT exerts in both periphery and brain. By studying the effect of the concentration and time of NT agonist exposure, two separate regulatory mechanisms were detected for the neurotensin receptor (NTR) gene in human colonic adenocarcinoma cells (HT-29).The incubation of cells for 6 h with the NT agonist, JMV 449, resulted in an increase of 270% in NTR mRNA levels. These changes were the direct result of new NTR gene transcription, as indicated by run-on and half-life experiments. In addition, the transcriptional activation of the NTR gene was dependent on NT-receptor complex internalization and de novo protein synthesis.A second response was detected with prolonged exposure to JMV 449. In this case, a decrease of 70% was detected in NTR mRNA levels. Unlike the initial phase, this change was mediated by a post-transcriptional event as the half-life of NTR mRNA from treated cells decreased by 50% as compared with control cells.NT agonist appears to regulate the synthesis of NTR mRNA. In HT-29 cells, this feedback is exerted by a biphasic response. These phases are apparently independent and mediated by two separate mechanisms. Neurotensin (NT)1 is a tridecapeptide, widely distributed in the central nervous system and peripheral tissues, exerting multiple functions (1). In the central nervous system, NT is a neurotransmitter as well as a neuromodulator of other neurotransmitters such as dopamine, acetylcholine, serotonin, and noradrenaline (2, 3). NT also possesses neuroendocrine actions inducing the release of several pituitary hormones (4). In the periphery, NT is secreted from mucosal endocrine cells of the small intestine into the circulation (5). In the gastrointestinal tract, NT causes many physiological effects including the stimulation of pancreatic secretion, the facilitation of colonic motility and fatty acid translocation, and tissue growth (6).In rat, NT actions are mediated by the stimulation of several specific receptors exhibiting high or low affinity for NT (7,8).The high affinity neurotensin receptor (NTR) is composed of 424 amino acids and belongs to the seven-transmembrane domain receptor family coupled to the G-proteins (7). The human NTR counterpart has also been cloned from human colonic adenocarcinoma cells (HT-29) (9). When HT-29 cells are challenged with a NT agonist, phosphatidylinositols are hydrolyzed leading to Ca 2ϩ mobilization (10). In contrast to N1E-115 cells, stimulation by NT in HT-29 cells is not associated with protein kinase C activation (10, 11).In addition to triggering cellular responses by specific ligands, receptors are often themselves regulated by their own agonists. In the case of NT, several studies have shown that variations in NTR expression were caused by changes in NT levels. For example, acute agonist stimulation of NTR induces desensitization and down-regulation of receptor in primary cultures of rat forebrain and HT-29 cells (12,13). Prolonged exposure of N1E-115 cells to N...

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Rapid agonist-induced decrease of neurotensin receptors from the cell surface in rat cultured neurons

Cited by 44 publications

References 31 publications

Synthesis of a biologically active fluorescent probe for labeling neurotensin receptors.

Synthesis of a biologically active fluorescent probe for labeling neurotensin receptors.

Neurotensin is a proinflammatory neuropeptide in colonic inflammation

Neurotensin Agonist Induces Differential Regulation of Neurotensin Receptor mRNA

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