Mediation of neurogenic ion transport by acetylcholine, prostanoids and 5-hydroxytryptamine in porcine ileum

Townsend, DeWayne; Casey, Melissa A.; Brown, David R.

doi:10.1016/j.ejphar.2005.07.023

Cited by 6 publications

(8 citation statements)

References 22 publications

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“…Mechanical stimulation of the mucosal surface leads to 5-HT release, which activates neurally mediated Cl - and bicarbonate secretion. The neurogenic secretory responses appear to be mediated primarily by 5-HT 3 and 5-HT 4 receptors, but 5-HT 1P receptors may also be involved 90, 91, 93–96 97 . Serotonin released from EC cells can also stimulate secretion through a direct paracrine action on nearby enterocytes, and this response is mediated by the activation of 5-HT 2 receptors 94 .…”

Section: Functions Of 5-ht In the Gastrointestinal Tractmentioning

confidence: 99%

Serotonin signalling in the gut—functions, dysfunctions and therapeutic targets

Mawe

Hoffman

2013

Nat Rev Gastroenterol Hepatol

839

783

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Serotonin (5-HT) has been recognized for decades as an important signaling molecule in the gut, but it is still revealing its secrets. We continue to discover novel gastrointestinal (GI) functions of 5-HT, as well as actions of gut-derived 5-HT outside of the gut, and we are learning how 5-HT signaling is altered in GI disorders. Furthermore, new therapeutic targets related to 5-HT signaling are being identified that can hopefully be exploited to alleviate the symptoms of functional GI disorders. Conventional functions of 5-HT in the gut involving intrinsic reflexes include stimulation of propulsive and segmentation motility patterns, epithelial secretion, and vasodilation. Activation of extrinsic vagal and spinal afferent fibers results in slowed gastric emptying, pancreatic secretion, satiation, pain and discomfort, as well as nausea and vomiting. Within the gut, 5-HT also exerts non-conventional actions that include serving as a pro-inflammatory signaling molecule and as a trophic factor to promote the development and maintenance of neurons and interstitial cells of Cajal. Platelet 5-HT, which comes from the gut, can promote hemostasis, influence bone development, and contribute to allergic airway inflammation. 5-HT3 receptor antagonists and 5-HT4 receptor agonists have been used to treat functional disorders with diarrhea or constipation, respectively. More recently, the synthetic enzyme, tryptophan hydroxylase has been targeted, and there are recent findings suggesting that epithelial 5-HT4 receptors could be targeted to provide a safe and effective treatment for constipation. Here we provide an overview of these serotonergic actions and treatment strategies.

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Section: Functions Of 5-ht In the Gastrointestinal Tractmentioning

confidence: 99%

Serotonin signalling in the gut—functions, dysfunctions and therapeutic targets

Mawe

Hoffman

2013

Nat Rev Gastroenterol Hepatol

839

783

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“…In rat and pig small intestine, 5-HT 2 , 5-HT 3 and 5-HT 4 receptor antagonists (ketanserin, ondansetron and tropisetron respectively) inhibit 5-HT-and cholera toxin-induced secretion (Kararli 1995, Hansen 1995, reviewed in Hansen & Skadhauge 1997, Townsend et al 2005. In rat and pig small intestine, 5-HT 2 , 5-HT 3 and 5-HT 4 receptor antagonists (ketanserin, ondansetron and tropisetron respectively) inhibit 5-HT-and cholera toxin-induced secretion (Kararli 1995, Hansen 1995, reviewed in Hansen & Skadhauge 1997, Townsend et al 2005.…”

Section: Serotonin Receptors In Intestinal Secretionmentioning

confidence: 99%

“…Three 5-HT receptors are generally accepted as being involved in 5-HT-induced intestinal secretion regardless of species (mouse, rat, pig and human) and intestinal segment (small and large intestine): epithelial 5-HT 2 and neuronal 5-HT 3 and 5-HT 4 receptors (Burleigh & Borman 1993, Siriwardena & Kellum 1993, Budhoo & Kellum 1994, Johnson et al 1994, Hansen 1995, Kararli 1995, Budhoo et al 1996a,b, Hansen & Skadhauge 1997, Townsend et al 2005). Furthermore, a fourth 5-HT receptor subtype, the 5-HT 1P , has been proposed to be of importance (Gershon 1999, Hansen 2003c).…”

Section: Serotonin Receptors In Intestinal Secretionmentioning

confidence: 99%

The role of serotonin in intestinal luminal sensing and secretion

2008

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This mini-review addresses the role of the neuroendocrine substance serotonin (5-hydroxytryptamine, 5-HT) in intestinal luminal sensing and secretion. Intestinal sensory neurones are activated by several mechanisms, in particular following stimulation of 'specialized' cells in the mucosa. These specialized cells are the enteroendocrine cells, which contain a wide variety of neuroendocrine transmitters. One of these enteroendocrine cells is the enterochromaffin (EC) cell, which is present throughout the intestines and contains large amounts of serotonin, predominantly in the duodenum in humans. The EC cells act as mucosal sensory transducers and secrete serotonin in response to various physiological and pathological luminal stimuli. Following release, serotonin participates in several mucosal protecting processes, one being secretion. Serotonin stimulates active ion, mucus and fluid secretion. Epithelial 5-HT(2) receptors and neuronal 5-HT(1P), 5-HT(3) and 5-HT(4) receptors mediate the secretory effect of serotonin. A transmembrane serotonin transporter terminates epithelial serotonergic signalling. The transient receptor potential ion channel family is important for processing intestinal luminal sensory signalling. Accumulating evidence suggests a significant interaction between serotonin and one of the transient receptor potential ion channels, the capsaicin-sensitive transient receptor potential vanilloid type 1. Accordingly, EC cells, serotonergic receptors and transporter(s), and transient receptor potential vanilloid type-1 ion channels are all explored as pharmacological targets for treatment of some intestinal functional disorders.

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“…Some investigators, based on the use of HEX, have implicated a small role for nAChR in the EFS response in whole thickness tissue (Hildebrand and Brown, 1990; Chandan et al , 1991a, 1991b). Thus, the majority of reports indicate that changes in epithelial ion transport as a consequence of ACh release (mimicked in vitro by EFS or application of exogenous cholinomimetics) are via mAChRs and pharmacological analyses do, in general, support the dogma that this is via epithelial M 3 and neuronal M 1 mAChRs (Cooke et al , 1983a; Cooke, 1984; Carey et al , 1987; Kuwahara et al , 1987a, 1987b; Diener et al , 1989; Traynor et al , 1991; Chandan et al , 1991a, 1991b; Javed and Cooke, 1992; O'Malley et al , 1995; Przyborski and Levin, 1997; Townsend et al , 2005). Stimulation of nAChRs does affect intestinal I SC , typically in full‐thickness tissue (i.e.…”

Section: Cholinergic Control Of Enteric Epithelial Ion Transportmentioning

confidence: 99%

Cholinergic regulation of epithelial ion transport in the mammalian intestine

Hirota

McKay

2006

British J Pharmacology

115

110

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Acetylcholine (ACh) is critical in controlling epithelial ion transport and hence water movements for gut hydration. Here we review the mechanism of cholinergic control of epithelial ion transport across the mammalian intestine. The cholinergic nervous system affects basal ion flux and can evoke increased active ion transport events. Most studies rely on measuring increases in short-circuit current (I SC ¼ active ion transport) evoked by adding ACh or cholinomimetics to intestinal tissue mounted in Ussing chambers. Despite subtle species and gut regional differences, most data indicate that, under normal circumstances, the effect of ACh on intestinal ion transport is mainly an increase in Cl -secretion due to interaction with epithelial M 3 muscarinic ACh receptors (mAChRs) and, to a lesser extent, neuronal M 1 mAChRs; however, AChR pharmacology has been plagued by a lack of good receptor subtype-selective compounds. Mice lacking M 3 mAChRs display intact cholinergically-mediated intestinal ion transport, suggesting a possible compensatory mechanism. Inflamed tissues often display perturbations in the enteric cholinergic system and reduced intestinal ion transport responses to cholinomimetics. The mechanism(s) underlying this hyporesponsiveness are not fully defined. Inflammation-evoked loss of mAChR-mediated control of epithelial ion transport in the mouse reveals a role for neuronal nicotinic AChRs, representing a hitherto unappreciated braking system to limit ACh-evoked Cl -secretion. We suggest that: i) pharmacological analyses should be supported by the use of more selective compounds and supplemented with molecular biology techniques targeting specific ACh receptors and signalling molecules, and ii) assessment of ion transport in normal tissue must be complemented with investigations of tissues from patients or animals with intestinal disease to reveal control mechanisms that may go undetected by focusing on healthy tissue only.

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Mediation of neurogenic ion transport by acetylcholine, prostanoids and 5-hydroxytryptamine in porcine ileum

Cited by 6 publications

References 22 publications

Serotonin signalling in the gut—functions, dysfunctions and therapeutic targets

Serotonin signalling in the gut—functions, dysfunctions and therapeutic targets

The role of serotonin in intestinal luminal sensing and secretion

Cholinergic regulation of epithelial ion transport in the mammalian intestine

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