A study of the concentrations of substance p and neurotensin in the gastrointestinal tract of various mammals

Holzer, Peter; Bucsics, A.; Saria, Alois; Lembeck, Fred

doi:10.1016/0306-4522(82)90114-2

Cited by 68 publications

(11 citation statements)

References 34 publications

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“…appearance of other biologically active substances in the organ bath or slow oxidation of substance P to substance P sulphoxide (Floor & Leeman, 1980). Appearance of substance P sulphoxide, which is much less active in contracting the ileum than substance P (Floor & Leeman, 1980), would have gone undetected by radioimmunoassay, since the antiserum used recognizes substance P and substance P sulphoxide to the same extent (Holzer, Bucsics, Saria & Lembeck, 1982). (ii) A second addition of substance P to the bath, after the response to the first exposure had largely faded away, failed to restore the initial peak contraction (Fig.…”

Section: Resultsmentioning

confidence: 99%

On the mechanism of contraction and desensitization induced by substance P in the intestinal muscle of the guinea‐pig.

Holzer¹,

Petsche²

1983

The Journal of Physiology

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SUMMARY1. The contractile effect of substance P on the longitudinal muscle of the isolated guinea-pig small intestine and the desensitization of the muscle which occurs on prolonged exposure to the peptide have been investigated. All experiments were performed in the presence of atropine.2. The response to a substance P concentration which produced a nearly maximal effect was not sustained but faded rapidly. It was found that not elimination of substance P from the bath, but desensitization of the muscle to substance P was the main cause for the fading of contraction.3. Desensitization of the muscle to substance P only developed if the muscle was exposed to the peptide for a certain time. The degree of and the time needed for recovery from desensitization were directly related to concentration of substance P and contact time.4. Tetraethylammonium (3 mM), which reduces the membrane conductance for K+, enhanced the potency of substance P in contracting the muscle and reduced the fading of contraction. Noradrenaline (295 nM), which increases the K+ conductance, produced opposite effects.5. Lowering the extracellular Ca2+ concentration to one-tenth decreased the potency of substance P in contracting the muscle, accelerated the fading of contraction, and reduced the ability of the muscle to respond to a second addition of substance P after the response to the first addition had faded away.6. Concentrations of substance P (22 nM) and tetraethylammonium (30 mM), which produced nearly maximal contractions, slightly enhanced the efflux of 86Rb from pre-loaded muscle strips. Both substances, however, caused a sustained reduction of 86Rb efflux from strips depolarized by high [K+], the effect of substance P being smaller than that of tetraethylammonium. The effect of substance P and tetraethylammonium on 86Rb efflux appeared independent of the extracellular [Ca2+].7. On exposure of the muscle to substance P (22 nM) for 8 min the intracellular uptake of 46Ca was first decreased and then increased while the 45Ca influx was instantly enhanced by tetraethylammonium (30 mM) or K+ (108 mM). The delayed increase in 45Ca influx caused by substance P was also observed in muscle strips depolarized with high [K+].-P. HOLZER AND U. PETSCHE 8. Taken together, the results suggest that there are two mechanisms of action by which substance P causes contraction of intestinal smooth muscle: reduction of a K+ conductance and a mechanism dependent on the extracellular [Ca2+]. Circumstantial evidence indicates that desensitization of the muscle to substance P arises from a block in excitation-contraction coupling and the hypothesis has been put forward that fading of the contractile response and desensitization reflect depletion of a Ca2+ store which is operated by the substance P receptor.

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Section: Resultsmentioning

confidence: 99%

On the mechanism of contraction and desensitization induced by substance P in the intestinal muscle of the guinea‐pig.

Holzer¹,

Petsche²

1983

The Journal of Physiology

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“…128,129 In the small intestine NT is produced by specialized cells, called N cells, that are localized among epithelial cells of the jejunum and ileum. 130 NT mediates its functions by binding to 2 specific G-protein coupled receptors, NT receptor 1 (NTR1) 131 and 2 (NTR2).…”

Section: Nt and Its Receptors In The Gi Tractmentioning

confidence: 99%

Role of neuropeptides in inflammatory bowel disease

Gross

Pothoulakis

2007

Inflammatory Bowel Diseases

149

128

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Inflammatory bowel disease (IBD) is a chronic, relapsing condition involving complex interactions between genes and the environment. The mechanisms triggering the initial attack and relapses, however, are not well understood. In the past several years the enteric nervous system (ENS) has been implicated in the pathophysiology of IBD. Both the ENS and the central nervous system (CNS) can amplify or modulate aspects of intestinal inflammation through secretion of neuropeptides that serve as a link between the ENS and CNS. Neuropeptides are defined as any peptide released from the nervous system that serves as an intercellular signaling molecule. Neuropeptides thought to play a potentially key role in IBD include substance P, corticotropin-releasing hormone, neurotensin, vasoactive intestinal peptide, mu-opioid receptor agonists, and galanin. This review focuses on the role of these neuropeptides in the pathophysiology of IBD and discusses the cell types and mechanisms involved in this process. The available evidence that neuropeptide blockade may be considered a therapeutic approach in both Crohn's disease and ulcerative colitis will also be discussed.

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“…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)(3)(4). NT has been identified in specific endocrine cells, named N-cells, in the ileal mucosa of dogs (5) and humans (6).…”

mentioning

confidence: 99%

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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A study of the concentrations of substance p and neurotensin in the gastrointestinal tract of various mammals

Cited by 68 publications

References 34 publications

On the mechanism of contraction and desensitization induced by substance P in the intestinal muscle of the guinea‐pig.

On the mechanism of contraction and desensitization induced by substance P in the intestinal muscle of the guinea‐pig.

Role of neuropeptides in inflammatory bowel disease

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

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