Analysis of the role of 5-HT in the enteric nervous system using anti-idiotopic antibodies to 5-HT receptors

1994 ◽  
Vol 266 (3) ◽  
pp. G403-G416 ◽  
Author(s):  
P. R. Wade ◽  
H. Tamir ◽  
A. L. Kirchgessner ◽  
M. D. Gershon
Keyword(s):  
Nervous System ◽  
Small Intestine ◽  
Substance P ◽  
Guinea Pig ◽  
Enteric Nervous System ◽  
Binding Sites ◽  
Input Resistance ◽  
Gastrointestinal Function ◽  
Postsynaptic Potentials

The effects of anti-idiotypic antibodies (alpha-id) that recognize serotonin [5-hydroxytryptamine (5-HT)] receptors on myenteric neurons of the guinea pig small intestine were characterized electrophysiologically, and alpha-id binding sites were located immunocytochemically. Initial applications of the alpha-id mimicked each of three actions of 5-HT: a rapid depolarization, associated with a fall in input resistance (Rin), which was inhibited by the 5-HT3 antagonists tropisetron (> or = 1 microM) and renzapride (100 microM); a slow membrane depolarization, associated with increased Rin, that was inhibited by the 5-HT1P antagonist renzapride but was unaffected by a 5-HT4 blocking concentration of tropisetron (10 microM); and a hyperpolarization, associated with decreased Rin, that was antagonized by the 5-HT1A inhibitor NAN-190. Cross-desensitization was observed between responses to 5-HT and the alpha-id. After exposure to the alpha-id, subsequent responses to the alpha-id, 5-HT, and stimulus-evoked slow excitatory postsynaptic potentials were antagonized; however, responses to carbachol and substance P were unaffected. The alpha-id thus specifically inhibits the effects of endogenously released and exogenously applied 5-HT. The alpha-id bound to sites on myenteric and submucosal neurons and a subepithelial nerve plexus. Binding of the alpha-id was blocked by 5-HT1P-, 5-HT3-, and 5-HT4-specific antagonists. We concluded that the alpha-id binds selectively to all known subtypes of 5-HT receptor in the enteric nervous system and is thus useful for investigating the gastrointestinal function of 5-HT.

Actions of cysteinyl leukotrienes in the enteric nervous system of guinea-pig stomach and small intestine

2003 ◽  
Vol 459 (1) ◽  
pp. 27-39 ◽  
Author(s):  
Sumei Liu ◽  
Hong-Zhen Hu ◽  
Chuanyun Gao ◽  
Na Gao ◽  
Guodu Wang ◽  
...  
Keyword(s):  
Nervous System ◽  
Small Intestine ◽  
Guinea Pig ◽  
Enteric Nervous System ◽  
Cysteinyl Leukotrienes ◽  
Guinea Pig Stomach

Evidence for a role of cholecystokinin as neurotransmitter in the guinea-pig enteric nervous system

1997 ◽  
Vol 236 (3) ◽  
pp. 155-158 ◽  
Author(s):  
Irma W.M Schutte ◽  
Kees B.C.W. Hollestein ◽  
Louis M.A Akkermans ◽  
Alfons B.A Kroese
Keyword(s):  
Nervous System ◽  
Guinea Pig ◽  
Enteric Nervous System

P2X7 receptors in the enteric nervous system of guinea-pig small intestine

2001 ◽  
Vol 440 (3) ◽  
pp. 299-310 ◽  
Author(s):  
Hong-Zhen Hu ◽  
Na Gao ◽  
Zhong Lin ◽  
Chuanyun Gao ◽  
Sumei Liu ◽  
...  
Keyword(s):  
Nervous System ◽  
Small Intestine ◽  
Guinea Pig ◽  
Enteric Nervous System ◽  
P2x7 Receptors

Role of glial cell-line derived neurotropic factor family receptor α2 in the actions of the glucagon-like peptides on the murine intestine

2007 ◽  
Vol 293 (2) ◽  
pp. G461-G468 ◽  
Author(s):  
Sean C. McDonagh ◽  
Jenny Lee ◽  
Angelo Izzo ◽  
Patricia L. Brubaker
Keyword(s):  
Nervous System ◽  
Substance P ◽  
Enteric Nervous System ◽  
Cell Line ◽  
Glial Cell ◽  
Wild Type ◽  
Intestinal Growth ◽  
Mrna Transcripts ◽  
Neurotropic Factor

The intestinal glucagon-like peptides GLP-1 and GLP-2 inhibit intestinal motility, whereas GLP-2 also stimulates growth of the intestinal mucosa. However, the mechanisms of action of these peptides in the intestine remain poorly characterized. To determine the role of the enteric nervous system in the actions of GLP-1 and GLP-2 on the intestine, the glial cell line-derived neurotropic factor family receptor α2 (GFRα2) knockout (KO) mouse was employed. The mice exhibited decreased cholinergic staining, as well as reduced mRNA transcripts for substance P-ergic excitatory motoneurons in the enteric nervous system (ENS) ( P < 0.05). Examination of parameters of intestinal growth (including small and large intestinal weight and small intestinal villus height, crypt depth, and crypt cell proliferation) demonstrated no differences between wild-type and KO mice in either basal or GLP-2-stimulated mucosal growth. Nonetheless, KO mice exhibited reduced numbers of synaptophysin-positive enteroendocrine cells ( P < 0.05), as well as a markedly impaired basal gastrointestinal (GI) transit rate ( P < 0.05). Furthermore, acute administration of GLP-1 and GLP-2 significantly inhibited transit rates in wild-type mice ( P < 0.05–0.01) but had no effect in GFRα2 KO mice. Despite these changes, expression of mRNA transcripts for the GLP receptors was not reduced in the ENS of KO animals, suggesting that GLP-1 and -2 modulate intestinal transit through enhancement of inhibitory input to cholinergic/substance P-ergic excitatory motoneurons. Together, these findings demonstrate a role for GFRα2-expressing enteric neurons in the downstream signaling of the glucagon-like peptides to inhibit GI motility, but not in intestinal growth.

scholarly journals Acute regulation of intestinal ion transport and permeability in response to luminal nutrients: the role of the enteric nervous system

2020 ◽  
Vol 318 (2) ◽  
pp. G254-G264
Author(s):  
Jean-Baptiste Cavin ◽  
Hailey Cuddihey ◽  
Wallace K. MacNaughton ◽  
Keith A. Sharkey
Keyword(s):  
Nervous System ◽  
Small Intestine ◽  
Ion Transport ◽  
Enteric Nervous System ◽  
Intestinal Permeability ◽  
Barrier Function ◽  
Enteric Neurons ◽  
Nerve Activity ◽  
Mouse Small Intestine

The small intestine regulates barrier function to absorb nutrients while avoiding the entry of potentially harmful substances or bacteria. Barrier function is dynamically regulated in part by the enteric nervous system (ENS). The role of the ENS in regulating barrier function in response to luminal nutrients is not well understood. We hypothesize that the ENS regulates intestinal permeability and ion flux in the small intestine in response to luminal nutrients. Segments of jejunum and ileum from mice were mounted in Ussing chambers. Transepithelial electrical resistance (TER), short-circuit current ( Isc), and permeability to 4-kDa FITC-dextran (FD4) were recorded after mucosal stimulation with either glucose, fructose, glutamine (10 mM), or 5% Intralipid. Mucosal lipopolysaccharide (1 mg/mL) was also studied. Enteric neurons were inhibited with tetrodotoxin (TTX; 0.5 μM) or activated with veratridine (10 μM). Enteric glia were inhibited with the connexin‐43 blocker Gap26 (20 μM). Glucose, glutamine, Intralipid, and veratridine acutely modified Isc in the jejunum and ileum, but the effect of nutrients on Isc was insensitive to TTX. TTX, Gap26, and veratridine treatment did not affect baseline TER or permeability. Intralipid acutely decreased permeability to FD4, while LPS increased it. TTX pretreatment abolished the effect of Intralipid and exacerbated the LPS‐induced increase in permeability. Luminal nutrients and enteric nerve activity both affect ion flux in the mouse small intestine acutely but independently of each other. Neither neuronal nor glial activity is required for the maintenance of baseline intestinal permeability; however, neuronal activity is essential for the acute regulation of intestinal permeability in response to luminal lipids and lipopolysaccharide. NEW & NOTEWORTHY Luminal nutrients and enteric nerve activity both affect ion transport in the mouse small intestine acutely, but independently of each other. Activation or inhibition of the enteric neurons does not affect intestinal permeability, but enteric neural activity is essential for the acute regulation of intestinal permeability in response to luminal lipids and lipopolysaccharide. The enteric nervous system regulates epithelial homeostasis in the small intestine in a time-dependent, region- and stimulus-specific manner.

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