Influence of sumatriptan on gastric fundus tone and on the perception of gastric distension in man

Tack, Jan; Coulie, Bernard; Wilmer, Alexander; Andrioli, A; Janssens, Jozef

doi:10.1136/gut.46.4.468

Cited by 201 publications

(185 citation statements)

References 24 publications

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“…In vitro, as in vivo, sumatriptan contracted the murine fundus, and the contraction was inhibited by GR-127935 and BRL-15572 pretreatment. The contractile effect of sumatriptan on the murine fundus seen in vivo (29) and in this study is in contrast to the relaxatory effect seen in humans and cats (11,24), suggesting a species-specific effect of sumatriptan. In muscle strip experiments, a 5-HT-induced contraction in the fundus has been previously described in several species (8 -10, 17, 22).…”

Section: Discussioncontrasting

confidence: 53%

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Serotonergic modulation of murine fundic tone

Lü

Camilleri²,

Locke³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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Fundic tone is maintained through a balance of excitatory and inhibitory input to fundic smooth muscle. The aim of this study was to determine the role of serotonin (5-HT) and 5-HT receptors in modulating murine fundic tone. Muscle strips were prepared from the murine fundus. Intracellular recordings were made from circular smooth muscle cells, and the effects of 5-HT on tone and excitatory and inhibitory junction potentials evoked by electrical field stimulation (EFS) were determined. 5-HT induced a concentration-dependent contraction and smooth muscle depolarization that was tetrodotoxin resistant. The 5-HT 1B/D receptor antagonists GR-127935 and BRL-155172 significantly inhibited 5-HT-induced contractions. The 5-HT 1B/D agonist sumatriptan contracted murine fundic muscle. The 5-HT 1A receptor agonist buspirone relaxed fundic smooth muscle, and the relaxation was inhibited by WAY-100135 but not by N -nitro-L-arginine or tetrodotoxin. 5-HT enhanced both the excitatory and inhibitory responses to EFS. The 5-HT 3 receptor antagonist MDL-72222 partly inhibited both the excitatory and inhibitory response elicited by EFS, whereas the 5-HT 4 receptor antagonist GR-113808 partly inhibited the EFS-evoked inhibitory response. The 5-HT reuptake inhibitor fluoxetine contracted smooth muscle strips, a contraction that was partially inhibited by GR-127935 and abolished by tetrodotoxin. In conclusion, the data suggest that 5-HT modulates murine fundic contractile activity through several different receptor subtypes. Sustained release of 5-HT maintains fundic tone through postjunctional 5-HT 1B/D receptors. 5-HT 3 receptors modulate excitatory neural input to murine fundic smooth muscle, and both 5-HT 3 and 5-HT4 receptors modulate inhibitory neural input to murine fundic smooth muscle.receptors; smooth muscle; enteric nerves; fundic accommodation; serotonin THE STOMACH WALL relaxes to accommodate the entry of content. Relaxation allows the accommodation of a large volume of content without a marked increase in intragastric pressure (7,15). Although there is evidence that the antrum accommodates after a meal, gastric accommodation occurs predominantly in the proximal stomach, especially in the fundus. The fundic integrated relaxatory response to a meal is known as fundic accommodation. The accommodation response is mediated through an extrinsic vagovagal reflex pathway and a nonvagal intrinsic reflex pathway. Both pathways act on intrinsic noncholinergic, nonadrenergic (NANC) neurons in the fundus and other parts of the stomach wall to relax smooth muscle cells (1,3,26,28). In the fasted state, well-established mediators of gastric fundic tone are vagally mediated cholinergic input (2, 29) and NANC inhibitory input (11, 12). The regulation of fundic tone is also mediated through serotonin (5-HT). In humans, sumatriptan, a 5-HT 1B/D agonist, relaxes the fundus (24, 25). In mice, in vivo, buspirone relaxed the fundus, whereas sumatriptan contracted it (29). There are two sources for 5-HT in the gut: release from enterochromaffi...

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Section: Discussioncontrasting

confidence: 53%

“…The regulation of fundic tone is also mediated through serotonin (5-HT). In humans, sumatriptan, a 5-HT 1B/D agonist, relaxes the fundus (24,25). In mice, in vivo, buspirone relaxed the fundus, whereas sumatriptan contracted it (29).…”

mentioning

confidence: 99%

Serotonergic modulation of murine fundic tone

Lü

Camilleri²,

Locke³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Shown are *P Ͻ 0.05, †P Ͻ 0.01. tion (35). Sumatriptan, a 5-HT 1 agonist, also induces relaxation of gastric fundus in humans (34).…”

Section: Discussionmentioning

confidence: 99%

Regional gastric contractility alterations in a diabetic gastroparesis mouse model: effects of cholinergic and serotoninergic stimulation

James¹,

Ryan²,

Crowell³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Regional gastric contractility alterations in a diabetic gastroparesis mouse model: effects of cholinergic and serotoninergic stimulation. Am J Physiol Gastrointest Liver Physiol 287: G612-G619, 2004. First published April 23, 2004 10.1152/ ajpgi.00431.2003.-The C57BLKS/J db/db mouse develops hyperglycemia and has delayed gastric emptying that is improved with tegaserod, a partial 5-HT4 agonist. Our aims here were to determine regional gastric contractility alterations in C57BLKS/J db/db mice and to determine the effects of serotonin and tegaserod. The contractile effects of bethanechol, serotonin, and tegaserod in fundic, antral, and pyloric circular muscle were compared in C57BLKS/J db/db mice and normal littermates. The effects of tetrodotoxin, atropine, and 5-HT receptor antagonists were studied. Contractions in response to bethanechol were decreased in the fundus, similar in the antrum, but increased in the pylorus in diabetic mice compared with controls. Serotonin and, to a lesser extent, tegaserod caused contractions that were more pronounced in the fundus than in the antrum and pylorus in both diabetic and normal mice. Serotonin-induced contractions were partially inhibited by atropine, the 5-HT4 antagonist GR113808, and the 5-HT2 antagonist cinanseron but not tetrodotoxin. Regional gastric contractility alterations are present in this diabetic gastroparesis mouse model. Fundic contractility was decreased, but pyloric contractility was increased in the pylorus to cholinergic stimulation in diabetic mice. Serotonin's contractile effect is mediated, in part, through muscarinic, 5-HT2, and 5-HT4 receptors. This study suggests that fundic hypomotility and pyloric hypercontractility, rather than antral hypomotility, play important roles for the gastric dysmotility that occurs in diabetes.serotonin; tegaserod GASTROPARESIS (delayed gastric emptying) is frequent in diabetic patients. It is a well-recognized complication of longstanding diabetes. Although classically, gastroparesis occurs in insulin-dependent diabetic patients, it also develops in type 2 (T2DM) or non-insulin-dependent diabetes mellitus (15). Gastroparesis is associated with antral hypomotility and perhaps pyloric dysfunction (2, 23).Treatment of gastroparesis is with prokinetic agents, which accelerate gastric emptying. Tegaserod, an aminoguanidine indole compound, is a recently developed 5-HT 4 partial agonist (1). Activation of 5-HT 4 receptors triggers the release of neurotransmitters from the enteric nerves resulting in increased contractility and stimulation of the peristaltic reflex (10). Tegaserod has been shown to accelerate gastric emptying in some (6) but not all studies (28).Strains of rats and mice with spontaneously developing hyperglycemia have been recognized as useful models to study the effects of diabetes. The Jackson Laboratory C57BLKS/J db/db mouse spontaneously develops hyperglycemia (12) and is a model for non-insulin-dependent diabetes mellitus (24). Prior studies in this mouse strain (22) have shown delayed gastric em...

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“…To evaluate the effect of duodenal infusion on the phasic contractility of the fundus, which corresponds to slow changes in baseline volume after filtering out respiratory artefact, a baseline reconstruction was performed by using a computerized algorithm (2). Consecutively, a motility index (MI) was calculated as the area between the signal and the baseline normalized over time (26). MI values were calculated for consecutive 5-min intervals during the distending periods at MDP ϩ 2 mmHg.…”

Section: Methodsmentioning

confidence: 99%