Expression and function of 5-HT<sub>4</sub>receptors in the mouse enteric nervous system

Liu, Mintsai; Geddis, Matthew S.; Wen, Ying; Setlik, Wanda; Gershon, Michael D.

doi:10.1152/ajpgi.00245.2005

Cited by 117 publications

(139 citation statements)

References 89 publications

(139 reference statements)

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“…and Park H., personal communication, 2006). The densities of 5-HT4 receptors were markedly higher in the myenteric and submucosal plexus than in the muscle layers and mucosa in the mouse bowel (Liu et al, 2005). Mosapride did not affect the spontaneous motility of the rectum and IAS, although a recent study by Liu et al (2005) reported that 5-HT4 receptors were also expressed in the mouse ileum ICC-MY.…”

Section: A Specific Enteric 5-ht4 Receptor Agonist Mosapride Enhancmentioning

confidence: 84%

“…A number of sub-types of 5-HT receptors are known to be expressed by enteric neurons, including the 5-HT1A, 5-HT2A, 5-HT2B, 5-HT3, and 5-HT4 sub-types (Liu et al, 2005). In addition, the 5-HT1P sub-type has also been identified in the enteric nervous system (ENS) Branchek et al, 1988;Mawe et al, 1986).…”

Section: -Ht Receptorsmentioning

confidence: 99%

“…Since the discovery of 5-HT4 receptors in 1988, significant advances have been made in our understanding of their physiology and pharmacology. The 5-HT4 receptor is a member of the seven transmembrane spanning G-protein-coupled family of receptors (Liu et al, 2005). The 5-HT4 receptor is thought to be coupled by Gs to the stimulation of adenylyl cyclase, increase in cAMP, and activation of PKA (Bender et al, 2000;Bockaert et al, 1990;Liu et al, 2005).…”

Section: -Ht Receptorsmentioning

confidence: 99%

“…The 5-HT4 receptor is a member of the seven transmembrane spanning G-protein-coupled family of receptors (Liu et al, 2005). The 5-HT4 receptor is thought to be coupled by Gs to the stimulation of adenylyl cyclase, increase in cAMP, and activation of PKA (Bender et al, 2000;Bockaert et al, 1990;Liu et al, 2005). The 5-HT4 receptor is pharmacologically defined by selective agonists such as SC 53116 and RS 67506, and selective antagonists such as GR 113808, SB 204070 and RS 39604 (Gale et al, 1994;Hegde et al, 1996).…”

Section: -Ht Receptorsmentioning

confidence: 99%

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Enhancement of the intrinsic defecation reflex by mosapride, a 5-HT4 agonist, in chronically lumbosacral denervated guinea pigs

Kojima

Fujii

Katsui

et al. 2006

J. Smooth Muscle Res.

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The defecation reflex is composed of rectal distension-evoked rectal (R-R) reflex contractions and synchronous internal anal sphincter (R-IAS) reflex relaxations in guinea pigs. These R-R and R-IAS reflexes are controlled via extrinsic sacral excitatory nerve pathway (pelvic nerves), lumbar inhibitory nerve pathways (colonic nerves) and by intrinsic cholinergic excitatory and nitrergic inhibitory nerve pathways. The effect of mosapride (a prokinetic benzamide) on the intrinsic reflexes, mediated via enteric 5-HT4 receptors, was evaluated by measuring the mechanical activity of the rectum and IAS in anesthetized guinea pigs using an intrinsic R-R and R-IAS reflex model resulting from chronic (two to nine days) lumbosacral denervation (PITH). In this model, the myenteric plexus remains undamaged and the distribution of myenteric and intramuscular interstitial cells of Cajal is unchanged. Although R-R and R-IAS reflex patterns markedly changed, the reflex indices (reflex pressure or force curve-time integral) of both the R-R contractions and the synchronous R-IAS relaxations were unchanged. The frequency of the spontaneous R and IAS motility was also unchanged. Mosapride (0.1-1.0 mg/kg) dose-dependently increased both intrinsic R-R (maximum: 1.82) and R-IAS reflex indices (maximum: 2.76) from that of the control (1.0) 6-9 days following chronic PITH. The dose-response curve was similar to that in the intact guinea pig, and had shifted to the left from that in the guinea pig after acute PITH. A specific 5-HT4 receptor antagonist, GR 113808 (1.0 mg/kg), decreased both reflex indices by approximately 50% and antagonized the effect of mosapride 1.0 mg/kg. This was quite different from the result in the intact guinea pig where GR 113808 (1.0 mg/kg) did not affect either of the reflex indices. The present results indicate that mosapride enhanced the intrinsic R-R and R-IAS reflexes and functionally compensated for the deprivation of extrinsic innervation. The actions of mosapride were mediated through endogenously active, intrinsic 5-HT4 receptors which may be post-synaptically located in the myenteric plexus of the anorectum.

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Section: A Specific Enteric 5-ht4 Receptor Agonist Mosapride Enhancmentioning

confidence: 84%

Section: -Ht Receptorsmentioning

confidence: 99%

Section: -Ht Receptorsmentioning

confidence: 99%

Section: -Ht Receptorsmentioning

confidence: 99%

See 2 more Smart Citations

Enhancement of the intrinsic defecation reflex by mosapride, a 5-HT4 agonist, in chronically lumbosacral denervated guinea pigs

Kojima

Fujii

Katsui

et al. 2006

J. Smooth Muscle Res.

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“…Pharmacologic interest in 5-HT 4 receptors stems from specific investigative findings that enteric neurons express the mRNA transcript that encodes the 5-HT 4 receptor and that immunohistochemical methods show ENS neuronal surface expression of the receptor in mice and guinea pigs [84,85]. Exposure to 5-HT 4 receptor agonists enhances fast excitatory postsynaptic potentials at nicotinic synapses in ENS microcircuits of guinea pigs and mice [84,86,87]. Release of neurotransmitters associated with peristaltic propulsion (e.g., acetylcholine, substance P, vasoactive intestinal peptide, nitric oxide) is initiated by stimulation of 5-HT 4 receptors [88].…”

Section: Serotonergic 5-ht 4 Receptormentioning

confidence: 99%

Enteric Nervous System: Neuropathic Gastrointestinal Motility

Wood

2016

Dig Dis Sci

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Serotonin receptor diversity in the human colon: Expression of serotonin type 3 receptor subunits 5‐HT3C, 5‐HT3D, and 5‐HT3E

Kapeller

Möller

Lasitschka

et al. 2010

J of Comparative Neurology

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Since the first description of 5-HT 3 receptors more than 50 years ago, there has been speculation about the molecular basis of their receptor heterogeneity. We have cloned the genes encoding novel 5-HT3 subunits 5-HT3C, 5-HT3D, and 5-HT3E and have shown that these subunits are able to form functional heteromeric receptors when coexpressed with the 5-HT3A subunit. However, whether these subunits are actually expressed in human tissue remained to be confirmed. In the current study, we performed immunocytochemistry to locate the 5-HT3A as well as the 5-HT3C, 5-HT3D, and 5-HT3E subunits within the human colon. Western blot analysis was used to confirm subunit expression, and RT-PCR was employed to detect transcripts encoding 5-HT 3 receptor subunits in microdissected tissue samples. This investigation revealed, for the first time, that 5-HT3C, 5-HT3D, and 5-HT3E subunits are coexpressed with 5-HT3A in cell bodies of myenteric neurons. Furthermore, 5-HT3A and 5-HT3D were found to be expressed in submucosal plexus of the human large intestine. These data provide a strong basis for future studies of the roles that specific 5-HT 3 receptor subtypes play in the function of the enteric and central nervous systems and the contribution that specific 5-HT 3 receptors make to the pathophysiology of gastrointestinal disorders such as irritable bowel syndrome and dyspepsia.Keywords 5-HT receptor; 5-HT 3 ; ligand-gated ion channel; antibody; gastrointestinal tract Serotonin (5-hydroxytryptamine; 5-HT)-mediated signaling is important in bidirectional brain-gut interactions involved in cognition, emotions, and digestive function (Gershon and Tack, 2007). Most of the body's 5-HT (~95%) is produced and stored in enterochromaffin cells (EC) in the enteric mucosal epithelium; however, smaller stores of 5-HT are also present in the bowel in serotonergic neurons of the enteric nervous system (ENS), where 5-HT participates in both slow and fast neurotransmission (Gershon, 2004(Gershon, , 2005Gershon and Tack, 2007). After its release from EC cells or neurons, 5-HT stimulates the 5-HT 1 , 1 5-HT 2 , 5-HT 3 , 5-HT 4 , and 5-HT 7 subtypes of receptor, all of which are expressed in the gut. Animal studies have indicated that 5-HT activates submucosal intrinsic primary afferent neurons (IPANs) through 5-HT 1P receptors to initiate peristaltic reflexes (Pan and Gershon, 2000;Wade et al., 1994) and myenteric IPANs through 5-HT 3 receptors (Bertrand et al., 1997) to initiate giant migrating contractions (Karaus and Sarna, 1987;Nagakura et al., 2002;Sarna, 2007). 5-HT also stimulates 5-HT 4 receptors to increase secretion of acetylcholine and calcitonin gene-related peptide (CGRP;Grider, 2003). This 5-HT 4Copyright © 2010 Wiley-Liss, Inc.Correspondence to: Beate Niesler. 1 5-HT3 subunits and 5-HT 3 receptors are termed according to the Nomenclature Committee of the International Union of Pharmacology (NC-IUPHAR;Peters et al., 2010 (Liu et al., 2005;Pan and Galligan, 1994;Ren et al., 2008) and probably underlies the successful use of 5-HT...

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Expression and function of 5-HT₄receptors in the mouse enteric nervous system

Cited by 117 publications

References 89 publications

Enhancement of the intrinsic defecation reflex by mosapride, a 5-HT4 agonist, in chronically lumbosacral denervated guinea pigs

Enhancement of the intrinsic defecation reflex by mosapride, a 5-HT4 agonist, in chronically lumbosacral denervated guinea pigs

Enteric Nervous System: Neuropathic Gastrointestinal Motility

Serotonin receptor diversity in the human colon: Expression of serotonin type 3 receptor subunits 5‐HT3C, 5‐HT3D, and 5‐HT3E

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Expression and function of 5-HT4receptors in the mouse enteric nervous system

Cited by 117 publications

References 89 publications

Enhancement of the intrinsic defecation reflex by mosapride, a 5-HT4 agonist, in chronically lumbosacral denervated guinea pigs

Enhancement of the intrinsic defecation reflex by mosapride, a 5-HT4 agonist, in chronically lumbosacral denervated guinea pigs

Enteric Nervous System: Neuropathic Gastrointestinal Motility

Serotonin receptor diversity in the human colon: Expression of serotonin type 3 receptor subunits 5‐HT3C, 5‐HT3D, and 5‐HT3E

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Expression and function of 5-HT₄receptors in the mouse enteric nervous system