Jejunal fluid and electrolyte secretion in carcinoid syndrome

Donowitz, Mark; Binder, Henry J.

doi:10.1007/bf01070754

Cited by 74 publications

(29 citation statements)

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“…Previous studies have shown that 5-HT administration in vivo induces Cl Ϫ secretion in the rabbit small intestine (31) and acts as a mediator of diarrhea in patients with carcinoid syndrome associated with a net secretion of water and electrolytes (32). Therefore, these studies suggest an important role of 5-HT in modifying electrolyte transport process that could involve either stimulation of Cl Ϫ secretion or a decrease in Na ϩ and Cl -absorption.…”

Section: -Htmentioning

confidence: 87%

Involvement of c-Src and Protein Kinase Cδ in the Inhibition of Cl-/OH- Exchange Activity in Caco-2 Cells by Serotonin

Saksena

Gill

Tyagi

et al. 2005

Journal of Biological Chemistry

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The gastrointestinal tract is an important source of the endogenous amine, serotonin, mainly stored in the mucosal enterochromaffin cells and in the enteric nervous system (1). 5-HT1 is continuously released from the enterochromaffin cells in the intestinal mucosa into the portal circulation and the gut lumen in response to a variety of luminal stimuli such as change in pH or osmolarity and mechanical and chemical stimuli (2). 5-HT is an important neurotransmitter and intercellular messenger to modulate gastrointestinal functions (3). 5-HT has been shown to alter gastrointestinal motility (4), alter gastric acid secretion, and enhance intestinal secretions (1, 5). Most of the previous studies regarding the effects of serotonin on ion transport were mainly based on the electrophysiological data including short circuit current measurements and unidirectional fluxes. These studies showed that 5-HT stimulated electrogenic Cl Ϫ secretion and inhibited Na ϩ and Cl Ϫ absorption in the rat colon (6), jejunum (7), ileum (8), and guinea pig ileum (9). 5-HT has also been shown to inhibit the NaClabsorptive process in the rabbit ileum and gall bladder (10) but has no effect in rabbit and guinea pig colon (10, 11). Moreover, Sundaram et al. (12) have demonstrated that 5-HT inhibits Cl Ϫ /HCO 3 Ϫ exchange activity in villus cells and stimulates HCO 3 Ϫ secretion in crypt cells of the rabbit ileum. In contrast, 5-HT appears to have no significant effect on coupled NaCl absorption in the human jejunum (13).5-HT exerts its effects by binding to 5-HT receptors, which are distributed on the neuronal, muscular, and epithelial structures (14). Based on pharmacological studies and molecular cloning (15), the existence of at least seven 5-HT receptors (5-HT1-7) subdivided into 14 subtypes has been discovered. With the exception of 5-HT5 and 5-HT6, 5-HT1 A , 5-HT1 P , 5-HT2, 5-HT3, and 5-HT4 have been reported to be expressed in the gut (16). 5-HT1, 5-HT2, and 5-HT4 receptors are coupled via guanine nucleotide binding (G) proteins to their effectors, whereas 5-HT3 receptor is a ligand-gated ion channel permeable to anions and cations (17).

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Section: -Htmentioning

confidence: 87%

Involvement of c-Src and Protein Kinase Cδ in the Inhibition of Cl-/OH- Exchange Activity in Caco-2 Cells by Serotonin

Saksena

Gill

Tyagi

et al. 2005

Journal of Biological Chemistry

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“…14,15 Donowitz and Binder 17 have described increased intestinal secretion in patients with carcinoid diarrhea, which will also contribute to diarrhea. Therefore, these factors rather than abnormal rectal mechano-sensory function are likely the major causes of carcinoid diarrhea.…”

Section: Discussionmentioning

confidence: 99%

“…shown that patients with carcinoid diarrhea have intestinal hypersecretion 17 and faster than normal transit through the small intestine and the colorectum. [14][15][16] However, it is well known from other patient groups that frequent bowel movements may be associated with rectal hypersensitivity and increased rectal tone.…”

Section: Introductionmentioning

confidence: 99%

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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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“…1,2 However, evidence is accumulating on the importance of other mediators such as 5-hydroxytryptamine (5-HT) present in enterochromaf®n cells and acting through receptors in the enteric nervous system. 3 5-HT is known to be an intestinal secretagogue, 4,5 and raised concentrations of 5-HT are found in carcinoid syndrome 6 and in diarrhoea associated with morphine withdrawal. 7 The possibility that 5-HT may also be involved in CT-induced secretion was SUMMARY Background: 5-hydroxytryptamine type 3 receptor antagonists have been shown to reduce¯uid and electrolyte secretion or promote absorption in experimental models of small intestinal secretion.…”

Section: Introductionmentioning

confidence: 99%

In vivo effects of the 5‐HT₃ antagonist alosetron on basal and cholera toxin‐induced secretion in the human jejunum: a segmental perfusion study

Bearcroft

André

Farthing

1997

Aliment Pharmacol Ther

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Background:5‐hydroxytryptamine type 3 receptor antagonists have been shown to reduce fluid and electrolyte secretion or promote absorption in experimental models of small intestinal secretion. The aim of this study was to compare the effects of a single dose (4 mg) of the 5‐hydroxytryptamine type 3 receptor antagonist alosetron and placebo on jejunal fluid and electrolyte movement in humans under basal conditions (n=7) and following cholera toxin‐induced secretion (n=5) in a randomized, double‐blind, crossover design over two separate study periods.Methods:One hour after oral alosetron or placebo, jejunal intubation was performed. A 30 cm segment of jejunum, isolated by two occluding balloons, was exposed to 15 μg of purified cholera toxin for 2 h prior to triple lumen perfusion with a plasma electrolyte solution containing []> 14C]‐polyethylene glycol as a non‐absorbable volume marker. In the basal study, intestinal perfusion was performed without exposure to cholera toxin. Collection and analysis of the effluent from the jejunal segment allowed fluid and electrolyte movement to be calculated.Results:Alosetron treatment increased basal jejunal fluid absorption (median 5.1 mL/cm/h [interquartile range 4.2 to 7.1] compared with placebo (3.8 [3.6 to 4.3] P=0.028, two sided Wilcoxon matched pairs signed rank test)). However, following establishment of a secretory state by cholera toxin, alosetron failed to significantly promote absorption or reduce secretion (0.3 [−1.2 to 1.2] compared to placebo (−4.3 [−7.7 to −1.3] P=0.14)). Adverse events during the study, which included anorexia, nausea, dizziness and loose bowel movements, were not considered to be clinically important. There were no clinically significant changes in laboratory parameters.Conclusion:The 5‐hydroxytyptamine type 3 receptor antagonist, alosetron increased basal fluid absorption in normal human small intestine but failed to have a beneficial effect in cholera toxin‐induced secretion.

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Jejunal fluid and electrolyte secretion in carcinoid syndrome

Cited by 74 publications

References 30 publications

Involvement of c-Src and Protein Kinase Cδ in the Inhibition of Cl-/OH- Exchange Activity in Caco-2 Cells by Serotonin

Involvement of c-Src and Protein Kinase Cδ in the Inhibition of Cl-/OH- Exchange Activity in Caco-2 Cells by Serotonin

Rectal Mechano-sensory Function in Patients with Carcinoid Diarrhea

In vivo effects of the 5‐HT₃ antagonist alosetron on basal and cholera toxin‐induced secretion in the human jejunum: a segmental perfusion study

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Jejunal fluid and electrolyte secretion in carcinoid syndrome

Cited by 74 publications

References 30 publications

Involvement of c-Src and Protein Kinase Cδ in the Inhibition of Cl-/OH- Exchange Activity in Caco-2 Cells by Serotonin

Involvement of c-Src and Protein Kinase Cδ in the Inhibition of Cl-/OH- Exchange Activity in Caco-2 Cells by Serotonin

Rectal Mechano-sensory Function in Patients with Carcinoid Diarrhea

In vivo effects of the 5‐HT3 antagonist alosetron on basal and cholera toxin‐induced secretion in the human jejunum: a segmental perfusion study

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In vivo effects of the 5‐HT₃ antagonist alosetron on basal and cholera toxin‐induced secretion in the human jejunum: a segmental perfusion study