Intestinal Serotonin Release, Sensory Neuron Activation, and Abdominal Pain in Irritable Bowel Syndrome

被引：207

作者：

Cremon, Cesare ^{[1
,2
]}

Carini, Giovanni ^{[1
,2
]}

Wang, Bingxian ^{[3
]}

Vasina, Valentina ^{[4
]}

Cogliandro, Rosanna F. ^{[1
,2
]}

De Giorgio, Roberto ^{[1
,2
]}

Stanghellini, Vincenzo ^{[1
,2
]}

Grundy, David ^{[5
]}

Tonini, Marcello ^{[6
]}

De Ponti, Fabrizio ^{[4
]}

Corinaldesi, Roberto ^{[1
,2
]}

Barbara, Giovanni ^{[1
,2
]}

机构：

[1] Univ Bologna, Dept Clin Med, Bologna, Italy

[2] Univ Bologna, Ctr Appl Biomed Res, Bologna, Italy

[3] St Josephs Healthcare, McMaster Brain Body Inst, Hamilton, ON, Canada

[4] Univ Bologna, Dept Pharmacol, Bologna, Italy

[5] Univ Sheffield, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England

[6] Univ Pavia, Dept Forens Med Pharmacol & Toxicol, I-27100 Pavia, Italy

来源：

AMERICAN JOURNAL OF GASTROENTEROLOGY | 2011年 / 106卷 / 07期

关键词：

ENTEROCHROMAFFIN CELL HYPERPLASIA; RAT JEJUNUM; PLASMA; 5-HYDROXYTRYPTAMINE; ENTEROENDOCRINE CELLS; ULCERATIVE-COLITIS; GUINEA-PIGS; MAST-CELLS; DISORDERS; PREDOMINANT; TRANSPORTER;

D O I：

10.1038/ajg.2011.86

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

OBJECTIVES: Serotonin (5-hydroxytryptamine, 5-HT) metabolism may be altered in gut disorders, including in the irritable bowel syndrome (IBS). We assessed in patients with IBS vs. healthy controls (HCs) the number of colonic 5-HT-positive cells; the amount of mucosal 5-HT release; their correlation with mast cell counts and mediator release, as well as IBS symptoms; and the effects of mucosal 5-HT on electrophysiological responses in vitro. METHODS: We enrolled 25 Rome II IBS patients and 12 HCs. IBS symptom severity and frequency were graded 0-4. 5-HT-positive enterochromaffin cells and tryptase-positive mast cells were assessed with quantitative immunohistochemistry on colonic biopsies. Mucosal 5-HT and mast cell mediators were assessed by high-performance liquid chromatography or immunoenzymatic assay, respectively. The impact of mucosal 5-HT on electrophysiological activity of rat mesenteric afferent nerves was evaluated in vitro. RESULTS: Compared with HCs, patients with IBS showed a significant increase in 5-HT-positive cell counts (0.37 +/- 0.16 % vs. 0.56 +/- 0.26 %; P = 0.039), which was significantly greater in patients with diarrhea-predominant IBS vs. constipation-predominant IBS (P = 0.035). Compared with HCs, 5-HT release in patients with IBS was 10-fold significantly increased (P < 0.001), irrespective of bowel habit, and was correlated with mast cell counts. A significant correlation was found between the mucosal 5-HT release and the severity of abdominal pain (r(s) = 0.582, P = 0.047). The area under the curve, but not peak sensory afferent discharge evoked by IBS samples in rat jejunum, was significantly inhibited by the 5-HT 3 receptor antagonist granisetron (P < 0.005). CONCLUSIONS: In patients with IBS, 5-HT spontaneous release was significantly increased irrespective of bowel habit and correlated with mast cell counts and the severity of abdominal pain. Our results suggest that increased 5-HT release contributes to development of abdominal pain in IBS, probably through mucosal immune activation.

引用

页码：1290 / 1298

页数：9

共 49 条

[1]

Altered 5-hydroxytryptamine signaling in patients with constipation- and diarrhea-predominant irritable bowel syndrome [J].

Atkinson, W ;

Lockhart, S ;

Whorwell, PJ ;

Keevil, B ;

Houghton, LA .

GASTROENTEROLOGY, 2006, 130 (01) :34-43

[2]

Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome [J].

Barbara, G ;

Stanghellini, V ;

De Giorgio, R ;

Cremon, C ;

Cottrell, GS ;

Santini, D ;

Pasquinelli, G ;

Morselli-Labate, AM ;

Grady, EF ;

Bunnett, NW ;

Collins, SM ;

Corinalidesi, R .

GASTROENTEROLOGY, 2004, 126 (03) :693-702

[3]

New pathophysiological mechanisms in irritable bowel syndrome [J].

Barbara, G ;

De Giorgio, R ;

Stanghellini, V ;

Cremon, C ;

Salvioli, B ;

Corinaldesi, R .

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2004, 20 :1-9

[4]

Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome [J].

Barbara, Giovanni ;

Wang, Bingxian ;

Stanghellini, Vincenzo ;

De Giorgio, Roberto ;

Cremon, Cesare ;

Di Nardo, Giovanni ;

Trevisani, Marcello ;

Campi, Barbara ;

Geppetti, Pierangelo ;

Tonini, Marcello ;

Bunnett, Nigel W. ;

Grundy, David ;

Corinaldesi, Roberto .

GASTROENTEROLOGY, 2007, 132 (01) :26-37

[5]

Postprandial plasma 5-hydroxytryptamine in diarrhoea predominant irritable bowel syndrome: a pilot study [J].

Bearcroft, CP ;

Perrett, D ;

Farthing, MJG .

GUT, 1998, 42 (01) :42-46

[6]

Activation of Human Enteric Neurons by Supernatants of Colonic Biopsy Specimens From Patients With Irritable Bowel Syndrome [J].

Buhner, Sabine ;

Li, Qin ;

Vignali, Sheila ;

Barbara, Giovanni ;

De Giorgio, Roberto ;

Stanghellini, Vincenzo ;

Cremon, Cesare ;

Zeller, Florian ;

Langer, Rupert ;

Daniel, Hannelore ;

Michel, Klaus ;

Schemann, Michael .

GASTROENTEROLOGY, 2009, 137 (04) :1425-1434

[7]

Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial [J].

Camilleri, M ;

Northcutt, AR ;

Kong, S ;

Dukes, GE ;

McSorley, D ;

Mangel, AW .

LANCET, 2000, 355 (9209) :1035-1040

[8]

Camilleri M, 1999, ALIMENT PHARM THERAP, V13, P1149

[9]

Alterations in expression of p11 and SERT in mucosal biopsy specimens of patients with irritable bowel syndrome [J].

Camilleri, Michael ;

Andrews, Christopher N. ;

Bharucha, Adil E. ;

Carlson, Paula J. ;

Ferber, Irene ;

Stephens, Debra ;

Smyrk, Thomas C. ;

Urrutia, Raul ;

Aerssens, Jeroen ;

Thielemans, Leen ;

Gohlmann, Hinrich ;

Van den Wyngaert, Ilse ;

Coulie, Bernard .

GASTROENTEROLOGY, 2007, 132 (01) :17-25

[10]

Pharmacological and pharmacokinetic aspects of functional gastrointestinal disorders [J].

Camilleri, Michael ;

Bueno, Lionel ;

de Ponti, Fabrizio ;

Fioramonti, Jean ;

Lydiard, R. Bruce ;

Tack, Jan .

GASTROENTEROLOGY, 2006, 130 (05) :1421-1434

← 1 2 3 4 5 →