Human colonic mucosa possesses a mixed population of 5-HT receptors

Borman, Richard A.; Burleigh, David

doi:10.1016/0014-2999(96)00466-9

Cited by 37 publications

(38 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The NPY C terminus, upon which the GR231118 homodimer is based, evokes histamine release from rat peritoneal mast cells (Grundemar et al, 1994) by a non-Y receptor-mediated mechanism (Mousli et al, 1995). Thus, nonspecific actions of the dipeptide in mouse colon could include mast cell degranulation and subsequent release of secretagogues such as histamine and 5-HT (Keely et al, 1995;Borman and Burleigh, 1996). Under such circumstances, small Y 4 -mediated decreases in I sc induced by GR231118 would be easily masked by larger amine-mediated secretory responses.…”

Section: Discussionmentioning

confidence: 99%

Y₄ Receptors Mediate the Inhibitory Responses of Pancreatic Polypeptide in Human and Mouse Colon Mucosa

Tough¹,

Holliday²,

Cox³

2006

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Y₄ Receptors Mediate the Inhibitory Responses of Pancreatic Polypeptide in Human and Mouse Colon Mucosa

Tough¹,

Holliday²,

Cox³

2006

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…The location of 5-HT 2A receptors on enterocytes probably accounts for the ketanserin-sensitive ability of 5-HT to act directly on the epithelium to induce Cl Ϫ secretion, increase inositine trisphophate, and for the specific binding of 3 H-ketanserin (3,38,41,43,74). 5-HT has also been reported to increase the rate at which enterocyte precursors proliferate (81).…”

Section: Discussionmentioning

confidence: 99%

“…Enteric neuronal 5-HT receptors include 5-HT 1A (26,48,49,62), 5-HT 1P (6,59,64), 5-HT 2B (18), 5-HT 3 (15,25,42,59), and 5-HT 4 (36,37,62,80). Enteric members of the 5-HT 2 family are associated with smooth muscle, which they stimulate to contract (17,27,51,52,67), and epithelial cells, which they stimulate to secrete (3,38,41,43,74). The 5-HT 2B receptor, which was originally known as the rat fundus receptor because of its location on the smooth muscle of gastric rumen (10,11,20,54,56), has now been shown also to be expressed on intestinal neurons, to be developmentally regulated, and to promote the development of enteric neurons (18).…”

mentioning

confidence: 99%

5-HT_2Areceptors: location and functional analysis in intestines of wild-type and 5-HT_2Aknockout mice

Fiorica‐Howells¹,

Hen

Gingrich

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

105

View full text Add to dashboard Cite

. 5-HT2A receptors: location and functional analysis in intestines of wild-type and 5-HT2A knockout mice. Am J Physiol Gastrointest Liver Physiol 282: G877-G893, 2002. First published January 9, 2002 10.1152/ajpgi.00435.2001.-The distribution and function of the 5-hydroxytryptamine (5-HT2A) receptor were investigated in the intestines of wild-type (5-HT2A ϩ/ϩ) and knockout (5-HT2A Ϫ/Ϫ) mice. In 5-HT2A ϩ/ϩ mice, rats, and guinea pigs, 5-HT2A receptor immunoreactivity was found on circular and longitudinal smooth muscle cells, neurons, enterocytes, and Paneth cells. Muscular 5-HT2A receptors were concentrated in caveolae; neuronal 5-HT2A receptors were found intracellularly and on the plasma membranes of nerve cell bodies and axons. Neuronal 5-HT2A immunoreactivity was detected as early as E14 in ganglia, intravillus nerves, and the deep muscle plexus. The 5-HT2A Ϫ/Ϫ colon did not express 5-HT2A receptors and did not contract in response to exogenous 5-HT. 5-HT2A Ϫ/Ϫ enterocytes were smaller, Paneth cells fewer, and muscle layers thinner (and showed degeneration) compared with those of 5-HT2A ϩ/ϩ littermates. The 5-HT2A receptor may thus be required for the maintenance and/or development of enteric neuroeffectors and other enteric functions, although gastrointestinal and colonic transit times in 5-HT2A Ϫ/Ϫ and ϩ/ϩ mice did not differ significantly. serotonin receptors; intestinal motility; immunocytochemistry THE ENTERIC NERVOUS SYSTEM (ENS) is different from the autonomic innervation of other organs, because it can mediate coordinated behaviors of the gut without central nervous system input (28,32,53). The presence in the bowel of intrinsic primary afferent neurons (IPANs) enables the ENS to respond to luminal stimuli. Because no nerve fibers enter the lumen, Bü lbring and Crema (7) proposed that sensory transduction is transepithelial, involving the pressure-induced secretion of 5-HT from enterochromaffin (EC) cells to stimulate the mucosal processes of the submucosal IPANs that initiate reflexes. This hypothesis has since been confirmed, and EC cell-derived 5-HT is now thought to activate both peristaltic (21,36,37,47,50,63) and secretory reflexes (12,73).In addition to its role in the initiation of enteric reflexes, 5-hydroxytryptamine (5-HT) also functions in ganglionic neurotransmission within the ENS. A subset of myenteric interneurons is serotonergic (8,13,22,29,31,76,77); therefore, 5-HT antagonists can block peristaltic reflexes by inhibiting enteric serotonergic neurotransmission (46, 60, 82) as well as by interfering with the paracrine stimulation of IPANs. 5-HT from EC cells also plays a role in extrinsic sensation by stimulating extrinsic primary afferent nerves (2, 39, 40).The bowel contains an abundance of 5-HT receptor subtypes located on neurons, smooth muscle, and epithelial cells (24,25,30). Enteric neuronal 5-HT receptors include 5-HT 1A (26,48,49,62), 5-HT 1P (6, 59, 64), 5-HT 2B (18), 5-HT 3 (15,25,42,59), and 5-HT 4 (36,37,62,80). Enteric members of the 5-HT 2 family are associated with s...

show abstract

“…In the small intestine, 5-HT 4 receptors mediate mucosal secretion (Budhoo et al, 1996) and smooth muscle relaxation (Kuemmerle et al, 1995). Coming down to the large intestine, 5-HT 4 receptors were found on circular smooth muscle, mediating relaxation (Meulemans et al, 1995;McLean et al, 1995;Tam et al, 1994;Prins et al, 2000), and on the mucosa mediating secretion (Borman & Burleigh, 1996).…”

Section: Introductionmentioning

confidence: 99%

5‐HT₄ receptors on cholinergic nerves involved in contractility of canine and human large intestine longitudinal muscle

Prins

Akkermans

Lefebvre

et al. 2000

British J Pharmacology

View full text Add to dashboard Cite

1 5-HT 4 receptors mediate circular muscle relaxation in both human and canine large intestine, but this phenomenon alone can not explain the improvement in colonic motility induced by selective 5-HT 4 receptor agonists in vivo. We set out to characterize 5-HT 4 receptor-mediated e ects in longitudinal muscle strips of canine and human large intestine. 2 Electrical ®eld stimulation (EFS) was applied providing submaximal isotonic contractions. L-NOARG (0.1 mM) was continuously present in the organ bath to preclude nitric oxide-induced relaxation to EFS. 3 The selective 5-HT 4 receptor agonist prucalopride (0.3 mM) enhanced EFS-evoked contractions, that were antagonized in both preparations by the selective 5-HT 4 receptor antagonist GR 113808 (0.1 mM). The prucalopride-induced increase was present in canine ascending and descending colon, but absent in rectum. Regional di erences in response to prucalopride were not observed in human ascending and sigmoid colon and rectum. Incubation with atropine (1 mM) or tetrodotoxin (0.3 mM) inhibited EFS-induced contractions, which were then una ected by prucalopride (0.3 mM) in both tissues. 4 In the presence of methysergide (3 mM; both tissues) and granisetron (0.3 mM; only human tissues), 5-HT (0.3 mM) enhanced EFS-induced contractions, an e ect that was antagonized by GR 113808 (0.1 mM). In the presence of atropine or tetrodotoxin, EFS-induced contractions were inhibited, leaving 5-HT (0.3 mM) ine ective in both preparations. 5 This study demonstrates for the ®rst time that in human and canine large intestine, 5-HT 4 receptors are located on cholinergic neurones, presumably mediating facilitating release of acetylcholine, resulting in enhanced longitudinal muscle contractility. This study and previous circular muscle strip studies suggest that 5-HT 4 receptor agonism facilitates colonic propulsion via a coordinated combination of inhibition of circumferential resistance and enhancement of longitudinal muscle contractility.

show abstract

Human colonic mucosa possesses a mixed population of 5-HT receptors

Cited by 37 publications

References 8 publications

Y₄ Receptors Mediate the Inhibitory Responses of Pancreatic Polypeptide in Human and Mouse Colon Mucosa

Y₄ Receptors Mediate the Inhibitory Responses of Pancreatic Polypeptide in Human and Mouse Colon Mucosa

5-HT_2Areceptors: location and functional analysis in intestines of wild-type and 5-HT_2Aknockout mice

5‐HT₄ receptors on cholinergic nerves involved in contractility of canine and human large intestine longitudinal muscle

Contact Info

Product

Resources

About

Human colonic mucosa possesses a mixed population of 5-HT receptors

Cited by 37 publications

References 8 publications

Y4 Receptors Mediate the Inhibitory Responses of Pancreatic Polypeptide in Human and Mouse Colon Mucosa

Y4 Receptors Mediate the Inhibitory Responses of Pancreatic Polypeptide in Human and Mouse Colon Mucosa

5-HT2Areceptors: location and functional analysis in intestines of wild-type and 5-HT2Aknockout mice

5‐HT4 receptors on cholinergic nerves involved in contractility of canine and human large intestine longitudinal muscle

Contact Info

Product

Resources

About

Y₄ Receptors Mediate the Inhibitory Responses of Pancreatic Polypeptide in Human and Mouse Colon Mucosa

Y₄ Receptors Mediate the Inhibitory Responses of Pancreatic Polypeptide in Human and Mouse Colon Mucosa

5-HT_2Areceptors: location and functional analysis in intestines of wild-type and 5-HT_2Aknockout mice

5‐HT₄ receptors on cholinergic nerves involved in contractility of canine and human large intestine longitudinal muscle