Neurotensin stimulates exocytotic histamine secretion from rat mast cells and elevates plasma histamine levels.

Carraway, Robert E.; Cochrane, David E.; Lansman, Jeffry B.; Leeman, Susan E.; Paterson, Brett M.; Welch, H J

doi:10.1113/jphysiol.1982.sp014080

Cited by 170 publications

(98 citation statements)

References 38 publications

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“…We also demonstrated that NT can potently degranulate mast cells, releasing histamine and generating leukotrienes (7,8). Furthermore the nonpeptide NT receptor antagonist SR-48,692 specifically blocked mast cell histamine release in vivo and in vitro in response to NT (9).…”

Section: Discussionmentioning

confidence: 89%

“…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).…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neurotensin is a proinflammatory neuropeptide in colonic inflammation

Castagliuolo¹,

Wang²,

Valenick³

et al. 1999

J. Clin. Invest.

130

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“…4). Previous results showed that NT directly activated connective tissue mast cells to release histamine in vitro and in vivo (32).…”

Section: Discussionmentioning

confidence: 95%

A neurotensin antagonist, SR 48692, inhibits colonic responses to immobilization stress in rats.

Castagliuolo

Leeman

Bartolák‐Suki

et al. 1996

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

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We previously reported that short-term immobilization stress of rats causes increased colonic mucin release, goblet cell depletion, prostaglandin E2 secretion, and colonic mast cell activation, as well as increased colonic motility. The purpose of this study was to investigate whether neurotensin (NT), a peptide expressed in both brain and digestive tract, participates in these responses. Rats were pretreated with SR 48692 (1 mg/kg, i.p.), an NT antagonist, 15 min before immobilization (30 min). The administration of the antagonist significantly inhibited stress-mediated secretion of colonic mucin, prostaglandin E2, and a product of rat mast cells, rat mast cell protease II (P < 0.05), but did not alter the increase in fecal pellet output caused by immobilization stress. Immobilization stress also resulted in a quantifiable decrease in the abundance of NT receptor mRNA in rat colon compared with that in colonic tissues from nonimmobilized rats as measured by densitometric analysis of in situ hybridization studies (P < 0.03). We conclude that the peptide NT is involved in colonic goblet cell release and mucosal mast cell activation after immobilization stress.Neurotensin (NT), a 13-aa peptide originally isolated by Carraway and Leeman (1, 2), has a broad but discrete localization throughout the central nervous system and the digestive tract of animals and humans (2-4). NT has been identified in specific endocrine cells, named N-cells, in the ileal mucosa of dogs (5) and humans (6). The known intestinal effects of NT include stimulation of growth of small and large bowel, pancreas, and stomach (7-9); stimulation of small intestinal secretion (10); inhibition of small bowel and gastric motility (11); and stimulation of colonic motor activity (12). It is well-established that restraint of animals stimulated motility of the large intestine, as measured by colonic transit and fecal pellet output (13,14). We recently reported that restraint of rats causes increased mucin release, as measured by [3H]glucosamine incorporation and goblet cell depletion, prostaglandin E2 (PGE2) secretion, and mast cell activation in colonic explants (15).A number of observations suggest that NT may participate in stress-related responses. For example, central administration of NT in freely moving rats stimulates release of adrenocorticotropin hormone and corticosterone levels (16-18), indicating that it may be involved in the regulation of hypothalamic-pituitary-adrenal axis activity. Ceccatelli et al. also showed up-regulation of the NT precursor mRNA in the paraventricular nucleus of the hypothalamus after immobilization stress (19). Augeron et al. (20) reported that NT stimulates mucin secretion from a human colonic goblet cell line by a receptormediated mechanism. Because our data showed that immobilization stress also stimulated colonic goblet cell degranulation and mucin secretion from rat colon (15), we postulated that NT is involved in colonic mucin secretion as well in other colonic responses after immobilization stress.A...

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“…For Ca-free solutions, CaCl2 was omitted from the Locke solution and replaced by EGTA 0.5 mM. In some experiments, mast cells were preincubated for 2 h at 37°C in Cafree solution containing EGTA 1 mM (Cochrane & Douglas, 1974;Carraway et al, 1982). For the experiments, 450 1l aliquots of the cells in Locke were preincubated for 10 min at 37°C, the releasing agent added in a volume of 50 pl and the incubation continued for 5 min.…”

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confidence: 99%

Parallel secretion of endogenous 5‐hydroxytryptamine and histamine from mast cells stimulated by vasoactive peptides and compound 48/80

Carraway

Cochrane

Granier

et al. 1984

British J Pharmacology

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The peptides, neurotensin, substance P, somatostatin, and bombesin, several analogues and fragments of neurotensin and compound 48/80, all caused the secretion of both endogenous 5-hydroxytryptamine (5-HT) and histamine. There was no differential effect of any of the secretagogues tested on the secretion of 5-HT and histamine. Amitriptyline prevented the secretion of histamine in response to stimulation by neurotensin, substance P, somatostatin or compound 48/80 but was without effect on the secretion of endogenous 5-HT.

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Neurotensin stimulates exocytotic histamine secretion from rat mast cells and elevates plasma histamine levels.

Cited by 170 publications

References 38 publications

Neurotensin is a proinflammatory neuropeptide in colonic inflammation

Neurotensin is a proinflammatory neuropeptide in colonic inflammation

A neurotensin antagonist, SR 48692, inhibits colonic responses to immobilization stress in rats.

Parallel secretion of endogenous 5‐hydroxytryptamine and histamine from mast cells stimulated by vasoactive peptides and compound 48/80

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