Influence of acute serotonin reuptake inhibition on colonic sensorimotor function in man

Tack, Jan; Broekaert, Dorine; Corsetti, Maura; Fischler, Benjamin; Janssens, Jozef

doi:10.1111/j.1365-2036.2006.02724.x

Cited by 62 publications

(55 citation statements)

References 41 publications

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“…The effect of 5-HT on rectal compliance remains obscure and needs further study. 36,37 Contrary to our hypothesis, we found no difference in rectal compli- ance between patients with carcinoid diarrhea and healthy controls. Thus, our data speak strongly against an effect of 5-HT on rectal biomechanics in patients with NET.…”

Section: Discussioncontrasting

confidence: 56%

Rectal Mechano-sensory Function in Patients with Carcinoid Diarrhea

Gregersen

Brock

Haase

et al. 2016

J Neurogastroenterol Motil

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Background/AimsIn patients with neuroendocrine tumors, excessive production of serotonin and other amines may cause the carcinoid syndrome, which is mainly characterized by diarrhea and flushing. Little is known about the pathophysiology of carcinoid diarrhea. In several other groups of patients, diarrhea may be associated with rectal hypersensitivity and increased rectal tone. Therefore, the aim of the present study was to compare rectal sensitivity and compliance in patients with carcinoid diarrhea and in healthy subjects. MethodsTwelve patients (6 males, aged 54-78 years, median 65 years), with carcinoid diarrhea and 19 healthy subjects (7 males, aged 50-78 years, median 61 years) were included. Rectal mechanical and heat stimulation was used for assessment of rectal mechano-sensory properties. ResultsOverall, 5.3% higher temperatures were needed to elicit sensory responses in patients with carcinoid diarrhea than in healthy subjects (P = 0.015). Posthoc analyses revealed that the sensory threshold to heat was 48.1 ± 3.1 o C in patients vs 44.7 ± 4.7 o C in healthy subjects (P = 0.041). In contrast, patients and healthy subjects showed no overall differences in rectal sensory response to mechanical distension (P = 0.731) or rectal compliance (P = 0.990). ConclusionsPatients with carcinoid diarrhea have higher sensory thresholds to heat stimulation in comparison to healthy subjects, but normal rectal sensation to mechanical distension and normal compliance. Therefore, treatment of carcinoid diarrhea should aim at prolonging gastrointestinal transit and decreasing secretion, rather than modifying rectal mechano-sensory function.

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Section: Discussioncontrasting

confidence: 56%

Rectal Mechano-sensory Function in Patients with Carcinoid Diarrhea

Gregersen

Brock

Haase

et al. 2016

J Neurogastroenterol Motil

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“…Acute dosing with citalopram has also been shown to increase the colonic phasic motility and decrease colonic response to a meal in healthy subjects, as well as decreasing the oesophageal sensitivity to both the acid infusion and distension. 55,56 The relevance of such acute effects on physiological readouts for clinical benefit from chronic treatment with these compounds is unknown.…”

Section: Serotonin Reuptake Inhibitorsmentioning

confidence: 99%

Review article: modulation of the brain–gut axis as a therapeutic approach in gastrointestinal disease

Mayer¹,

Tillisch²,

Bradesi³

2006

Aliment Pharmacol Ther

121

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SummaryBackgroundThe importance of bi‐directional brain‐gut interactions in gastrointestinal illness is increasingly being recognized, most prominently in the area of functional gastrointestinal disorders. Numerous current and emerging therapies aimed at normalizing brain–gut interactions are a focus of interest, particularly for irritable bowel syndrome and functional dyspepsia.MethodsA literature search was completed for preclinical and clinical studies related to central modulation of gastrointestinal functions and published in English between 1980 and 2006.ResultsExisting data, while sparse, support the use of different classes of antidepressant drugs, including tricyclics, and selective and non‐selective serotonin reuptake inhibitors in irritable bowel syndrome. Serotonin receptor agonists and antagonists with peripheral and possibly central effects are effective in treating specific subtypes of irritable bowel syndrome. Based largely on theoretical and preclinical evidence, several novel compounds that selectively target receptors at multiple levels within the brain–gut axis such as neurokinin, somatostatin and corticotropin‐releasing factor receptor antagonists are promising.ConclusionsThis review discusses the rationale for modulation of the brain–gut axis in the treatment of functional gastrointestinal disorders and highlights the most promising current and future therapeutic strategies.

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“…Recent reports have confirmed the relevance of the SERT function for the control of intestinal activity [30,31]. SERT expression and activity are affected in intestinal inflammation [10,[14][15][16] and inflammatory mediators have been shown to inhibit SERT function and expression in epithelial cells [12,13].…”

Section: Discussionmentioning

confidence: 83%

Regulation of serotonin transporter activity by adenosine in intestinal epithelial cells

Matheus¹,

Mendoza²,

Iceta³

et al. 2009

Biochemical Pharmacology

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Serotonin plays a critical role in the regulation of intestinal physiology. The serotonin transporter (SERT) expressed in the intestinal epithelium determines 5-HT availability and activity. The serotoninergic system and SERT activity have been described as being altered in chronic intestinal pathologies such as inflammatory diseases. Adenosine has also been shown to be involved in a variety of intestinal functions and to play a central role in the regulation of inflammatory responses of injured tissue. Since the modulation of SERT by adenosine in the intestine remains unknown, the aim of the present work was to study the effect of adenosine on SERT activity and expression and to determine the molecular mechanism involved. The study has been carried out using human enterocyte-like Caco-2 cells which endogenously express SERT. The results show that adenosine diminishes SERT activity in both the apical and basal membranes by acting in the intrinsic molecule with no alteration of either SERT mRNA or protein levels. The effect of adenosine appears to be mediated by A 2 receptors and activation of the cAMP/PKA signalling pathway. Moreover, the adenosine effect did not seem to involve the activation of AMP activated protein kinase. Adenosine effects are reached at high concentrations, which suggests that adenosine modulation of SERT may be significant under conditions of inflammation and tissue injury.

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Influence of acute serotonin reuptake inhibition on colonic sensorimotor function in man

Abstract: SUMMARY BackgroundIt is unclear whether decreased serotonin transporter function contributes to sensorimotor abnormalities in irritable bowel syndrome.

Cited by 62 publications

References 41 publications

Rectal Mechano-sensory Function in Patients with Carcinoid Diarrhea

Rectal Mechano-sensory Function in Patients with Carcinoid Diarrhea

Review article: modulation of the brain–gut axis as a therapeutic approach in gastrointestinal disease

Regulation of serotonin transporter activity by adenosine in intestinal epithelial cells

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