Supernatants of irritable bowel syndrome mucosal biopsies impair human colonic smooth muscle contractility

Guarino, Michele Pier Luca; Barbara, Giovanni; Cicenia, Alessia; Altomare, Annamaria; Barbaro, Maria Raffaella; Cocca, Silvia; Scirocco, Annunziata; Cremon, Cesare; Emerenziani, Sara; Stanghellini, Vincenzo; Cicala, Michele; Severi, Carola

doi:10.1111/nmo.12928

Cited by 12 publications

(9 citation statements)

References 37 publications

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“…PA inhibited the CCh-induced contractions; thus, PA may regulate acetylcholine transmission by antagonizing the muscarinic receptor or nicotinic acetylcholine receptor. Cholinergic nerves were excited in colons of stress-induced IBS-D rats, which is consistent with the published data[ 29 ]. Pretreatment with a single PA concentration strongly inhibited the CCh-induced (1 × 10 −9 mol/L to 3 × 10 −7 mol/L) contractions in the IBS-D rat colon in vitro .…”

Section: Discussionsupporting

confidence: 92%

Inhibitory effects of patchouli alcohol on stress-induced diarrhea-predominant irritable bowel syndrome

Zhou

Huang

et al. 2018

WJG

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AIMTo elucidate the mechanism of patchouli alcohol (PA) in treatment of rat models of diarrhea-predominant irritable bowel syndrome (IBS-D).METHODSWe studied the effects of PA on colonic spontaneous motility using its cumulative log concentration (3 × 10−7 mol/L to 1 × 10−4 mol/L). We then determined the responses of the proximal and distal colon segments of rats to the following stimuli: (1) carbachol (1 × 10−9 mol/L to 1 × 10−5 mol/L); (2) neurotransmitter antagonists including Nω-nitro-L-arginine methyl ester hydrochloride (10 μmol/L) and (1R*, 2S*)-4-[2-Iodo-6-(methylamino)-9H-purin-9-yl]-2-(phosphonooxy)bicyclo[3.1.0]hexane-1-methanol dihydrogen phosphate ester tetraammonium salt (1 μmol/L); (3) agonist α,β-methyleneadenosine 5′-triphosphate trisodium salt (100 μmol/L); and (4) single KCl doses (120 mmol/L). The effects of blockers against antagonist responses were also assessed by pretreatment with PA (100 μmol/L) for 1 min. Electrical-field stimulation (40 V, 2-30 Hz, 0.5 ms pulse duration, and 10 s) was performed to observe nonadrenergic, noncholinergic neurotransmitter release in IBS-D rat colon. The ATP level of Kreb’s solution was also determined.RESULTSPA exerted a concentration-dependent inhibitory effect on the spontaneous contraction of the colonic longitudinal smooth muscle, and the half maximal effective concentration (EC50) was 41.9 μmol/L. In comparison with the KCl-treated IBS-D group, the contractile response (mg contractions) in the PA + KCl-treated IBS-D group (11.87 ± 3.34) was significantly decreased in the peak tension (P < 0.01). Compared with CCh-treated IBS-D rat colon, the cholinergic contractile response of IBS-D rat colonic smooth muscle (EC50 = 0.94 μmol/L) was significantly decreased by PA (EC50 = 37.43 μmol/L) (P < 0.05). Lack of nitrergic neurotransmitter release in stress-induced IBS-D rats showed contraction effects on colonic smooth muscle. Pretreatment with PA resulted in inhibitory effect on L-NAME-induced (10 μmol/L) contraction (P < 0.05). ATP might not be the main neurotransmitter involved in inhibitory effects of PA in the colonic relaxation of stress-induced IBS-D rats.CONCLUSIONPA application may serve as a new therapeutic approach for IBS-D.

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Section: Discussionsupporting

confidence: 92%

Inhibitory effects of patchouli alcohol on stress-induced diarrhea-predominant irritable bowel syndrome

Zhou

Huang

et al. 2018

WJG

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“…Segmental activity of the sigmoid colon decreased in patients with IBS-D, but increased in patients with IBS-C ( Clemens et al., 2003 ). Experimental studies have shown that colon supernatant from patients with IBS can weaken spontaneous and ACh-induced contraction of the isolated colonic smooth muscle, independent of IBS subtype ( Guarino et al., 2017 ). In addition to that of the colon, patients with IBS-D also experience dysfunction of small intestinal movement ( Kellow et al., 1999 ).…”

Section: Discussionmentioning

confidence: 99%

Shugan Decoction Alleviates Colonic Dysmotility in Female SERT-Knockout Rats by Decreasing M3 Receptor Expression

et al. 2020

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Background: Irritable bowel syndrome (IBS) is a functional gut disease characterized by visceral hypersensitivity and gut motor dysfunction. Serotonin (5-hydroxytryptamine, 5-HT) is an important enteric neurotransmitter. High levels of 5-HT aggravate IBS symptoms. The serotonin reuptake transporter (SERT) is a membrane-embedded transporter involved in IBS pathogenesis that plays an important role in regulating 5-HT signaling. Aim: We investigated whether gut motor function was altered in SERT-knockout (SERT-KO) rats. Additionally, we sought to determine whether Shugan decoction (SGD), a clinically experienced prescription for the treatment of IBS, exerts regulatory effects on intestinal motility in SERT-KO rats, and attempted to identify the mechanisms involved. Method: SERT-KO rats were produced by transcription activator-like effector nuclease (TALEN) technology. Fecal pellet output was measured for ten consecutive days to estimate distal colonic motility. Small intestinal motility was measured by charcoal-meal experiments. The colonic and small intestinal muscle contractile activities were measured by organ bath study. Western blot was used to analyze the muscarinic receptor expression in colon tissue.

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“…46,47 According to the study of Barbara et al, 43 the pronociceptive effect of histamine appears to be mediated, at least partly, by H 1 R expressed on sensory afferents. In contrast, Guarino et al 48 found that supernatants from patients with IBS impair contractility of isolated human colonic smooth muscles and the phenomenon is histamine-independent. The effect was significantly reversible by apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, suggesting the intracellular oxidative stress damage to be the main cause of this contractility impairment.…”

Section: -41mentioning

confidence: 99%

Targeting Histamine Receptors in Irritable Bowel Syndrome: A Critical Appraisal

Fabisiak

Włodarczyk

Fabisiak

et al. 2017

J Neurogastroenterol Motil

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Irritable bowel syndrome is a group of functional gastrointestinal disorders with not yet fully clarified etiology. Recent evidence suggesting that mast cells may play a central role in the pathogenesis of irritable bowel syndrome paves the way for agents targeting histamine receptors as a potential therapeutic option in clinical treatment. In this review, the role of histamine and histamine receptors is debated. Moreover, the clinical evidence of anti-histamine therapeutics in irritable bowel syndrome is discussed.

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Supernatants of irritable bowel syndrome mucosal biopsies impair human colonic smooth muscle contractility

Abstract: Supernatants from mucosal biopsies of IBS patients reduce colonic contractility. The observed impairment was concentration dependent, likely occurring through intracellular oxidative stress damage, involving different neuromotor mechanisms depending on the IBS subtype.

Cited by 12 publications

References 37 publications

Inhibitory effects of patchouli alcohol on stress-induced diarrhea-predominant irritable bowel syndrome

Inhibitory effects of patchouli alcohol on stress-induced diarrhea-predominant irritable bowel syndrome

Shugan Decoction Alleviates Colonic Dysmotility in Female SERT-Knockout Rats by Decreasing M3 Receptor Expression

Targeting Histamine Receptors in Irritable Bowel Syndrome: A Critical Appraisal

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