Characterization of the EP receptor types that mediate longitudinal smooth muscle contraction of human colon, mouse colon and mouse ileum

Fairbrother, Sian; Smith, Julia E.; Borman, Richard A.; Cox, Helen

doi:10.1111/j.1365-2982.2011.01727.x

Cited by 18 publications

(15 citation statements)

References 38 publications

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“…However, this data is taken from studies using human tissue therefore there may be difference across species. Nevertheless this EP 4 receptor antagonist has also been used in animal models (Fairbrother et al, 2011). NS-398 is one of the most commonly used COX-2 inhibitors in research investigating COX-2 inhibition in stroke models (Nogawa et al, 1997;Iadecola et al, 2001).…”

Section: Discussionmentioning

confidence: 97%

Neuroprotection mediated by the EP4 receptor avoids the detrimental side effects of COX-2 inhibitors following ischaemic injury

2013

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Section: Discussionmentioning

confidence: 97%

Neuroprotection mediated by the EP4 receptor avoids the detrimental side effects of COX-2 inhibitors following ischaemic injury

2013

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“…A host of studies have documented a role for cox-2 and its prostaglandin products in negatively regulating intestinal motility (Cong et al, 2007; Takechi et al, 2009; Fairbrother et al, 2011; Nylander, 2011; Shi et al, 2011). In addition, cox-2 activity positively regulates intestine macrophage infiltration in a rodent model of sepsis (Osterberg et al, 2006) perhaps offering an additional mechanism explaining why APP −/− mouse CD68 positive macrophage immunoreactivity was attenuated compared to wild type mice.…”

Section: Discussionmentioning

confidence: 99%

Amyloid Precursor Protein Expression Modulates Intestine Immune Phenotype

Puig

Swigost

Zhou

et al. 2011

J Neuroimmune Pharmacol

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Amyloid precursor protein (APP) is widely expressed across many tissue and cell types. Proteolytic processing of the protein gives rise to a plethora of protein fragments with varied biological activities. Although a large amount of data has been generated describing the metabolism of the protein in neurons, its role in regulating the phenotype of other cells remains unclear. Based upon prior work demonstrating that APP regulates the activation phenotype of monocytic lineage cells, we hypothesized that APP can regulate macrophage activation phenotype in tissues other than brain. Ileums of the small intestines from C57BL6/J wild type and APP−/− mice were compared as a representative tissue normally associated with abundant macrophage infiltration. APP−/− intestines demonstrated diminished CD68 immunoreactivity compared to wild type mice. This correlated with significantly less cycloxygenase-2 (cox-2), CD68, CD40, CD11c, and βIII-tubulin protein levels. Peritoneal macrophage from APP−/− mice demonstrated decreased in vitro migratory ability compared to wild type cells and diminished basal KC cytokine secretion. Whereas, APP−/− intestinal macrophage had an increase in basal KC cytokine secretion compared to wild type cells. Conversely, there was a significant decrease in multiple cytokine levels in APP−/− compared to wild type ileums. Finally, APP−/− mice demonstrated impaired absorption and increased motility compared to wild type mice. These data demonstrate the APP expression regulates immune cell secretions and phenotype and intestinal function. This data set describes a novel function for this protein or its metabolites that may be relevant not only for Alzheimer’s disease but a range of immune-related disorders.

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“…20 However, prostaglandin E 2 induces longitudinal smooth muscle contraction via the EP 1 receptor in the human colon. 21 Thus, the direct effect on the colon smooth muscle, and an activation of mucosal endings of myenteric and submucosal neurons have been suggested as a mechanism of action of bisacodyl. 22 Colonic HAPC is an important mechanism for facilitating the transit of colonic contents over long distances, and often precedes defecation.…”

Section: Discussionmentioning

confidence: 99%

Increased Tone of the Human Colon Muscle by Bisacodyl In Vitro

Kim

et al. 2018

J Neurogastroenterol Motil

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Background/AimsAlthough bisacodyl is a widely administered laxative, its underlying mechanism of action remains generally unknown. This study focuses on investigating the effects of bisacodyl on the human colon muscle contraction, and elucidating its mechanism of action.MethodsSigmoid colon muscle strips (20 longitudinal and 18 circular muscles) were obtained from 20 subjects who underwent colectomy for colon cancer. Isometric force measurements were calculated in response to electrical field stimulation (EFS, 0.3 milliseconds in trains of 10 Hz for 20 seconds, 150 V). Peak and nadir (tone) during and after EFS, were measured in a controlled state, and after sequential addition of bisacodyl (1 μM), atropine (1 μM), N-nitro-L-arginine (L-NNA, 100 μM), MRS2500 (1 μM), and tetrodotoxin (TTX, 1 μM) to the organ bath.ResultsTransient phasic contractions were observed during EFS, and after cessation of EFS. In the longitudinal muscles, nadir during EFS, and tone after EFS, significantly increased after addition of bisacodyl, and persisted after sequential addition of atropine, L-NNA, MRS2500, and TTX, indicating a direct action of bisacodyl on the smooth muscle. In the second experiment, pretreatment of TTX abolished EFS-induced phasic contractions. Although no phasic contraction was produced after perfusion of bisacodyl, tone was increased, thereby supporting evidence of a direct mechanism of action of bisacodyl on the colon smooth muscle.ConclusionsBisacodyl increases the tone of longitudinal muscle in the human sigmoid colon through a direct action on the smooth muscle. Further study is warranted to investigate the neural mechanism of action of bisacodyl.

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Characterization of the EP receptor types that mediate longitudinal smooth muscle contraction of human colon, mouse colon and mouse ileum

Abstract: PGE(2) -induced contraction of longitudinal smooth muscle is mediated by EP(1) receptors in human colon and by a combination of EP(1) and EP(3) receptors in mouse intestine, whereas EP(2) receptors modulate relaxation in all three preparations.

Cited by 18 publications

References 38 publications

Neuroprotection mediated by the EP4 receptor avoids the detrimental side effects of COX-2 inhibitors following ischaemic injury

Neuroprotection mediated by the EP4 receptor avoids the detrimental side effects of COX-2 inhibitors following ischaemic injury

Amyloid Precursor Protein Expression Modulates Intestine Immune Phenotype

Increased Tone of the Human Colon Muscle by Bisacodyl In Vitro

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