Identification and distribution of 5‐HT<sub>3</sub> recognition sites in the rat gastrointestinal tract

Champaneria, Shashi; Costall, B.; Naylor, R.J.; Robertson, David W.

doi:10.1111/j.1476-5381.1992.tb14396.x

Cited by 33 publications

(10 citation statements)

References 24 publications

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“…The 5-HT3 antagonist granisetron (Sanger & Nelson 1989) abolished the response of the proximal colon to 2-Me-5-HT, but failed to influence the ability of 5-HT to increase the SCC in this region (Fig. 4, Table 4), although the higher concentration used exceeded that ( M) shown to abolish binding to 5-HT3-recognition sites in the rat gastrointestinal tract (Champaneria et al 1992). In the distal colon, granisetron did not inhibit the response to 5-HT and at the higher concentration (1.4 x M) it reduced the EC5O (Table 4); it also caused a concentration-dependent increase in the maximum response, although this just failed to reach significance (Table 4).…”

Section: A -~-A -~~~L~-a -A -mentioning

confidence: 92%

Comparison of the Secretory Actions of 5-Hydroxytryptamine in the Proximal and Distal Colon of the Rat

Ayton

Hardcastle

et al. 1995

Journal of Pharmacy and Pharmacology

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The ability of 5‐hydroxytryptamine (5‐HT) to induce a secretory response in rat proximal and distal colon was examined both in‐vivo and in‐vitro by measuring transintestinal electrical activity. In‐vivo 5‐HT caused a dose‐dependent increase in the potential difference (PD) in both regions of the colon (maximum PD change = 7·2 ± 0·5 (n = 17)mV in proximal colon and 9·2 ± 0·7 (n = 17)mV in distal colon), an effect that was also observed in stripped (outer muscle layers removed) colonic sheets where the PD change was found to result from a rise in short‐circuit current (SCC, maximum change = 150 ± 24 (n = 15)μA cm−2 in proximal colon and 126 ± 10 (n = 19)μA cm−2 in distal colon). The effects of 2‐methyl‐5‐hydroxytryptamine (2‐Me‐5‐HT), a relatively selective agonist at 5‐HT3 receptors, and 5‐methoxytryptamine (5‐MT), an agonist at all 5‐HT receptors except 5‐HT3, were also tested, their specificity of action being confirmed by their actions on cardiovascular function in‐vivo. 2‐Me‐5‐HT produced a similar response to 5‐HT in proximal colon, but was less effective in the distal region, particularly in‐vitro where it failed to induce any significant change in electrical activity. In contrast, 5‐MT was more effective in the distal colon. Frusemide (10−3 M) inhibited the rise in SCC induced by both 2‐Me‐5‐HT and 5‐MT, indicating that, like 5‐HT, these agonists stimulated electrogenic Cl· secretion. The 5‐HT3 antagonist granisetron abolished the effects of 2‐Me‐5‐HT, both in‐vivo (8·6 times 10−8 molkg−1) and in‐vitro (1·4 times 10−6M, 1·4 times 10−4M), but only caused a slight inhibition of the response to 5‐HT in‐vivo and no inhibition at all in stripped colonic sheets. It is concluded that although 5‐HT induces a secretory response in both proximal and distal colon, the mechanisms responsible differ, with 5‐HT3 receptors making a greater contribution in the proximal region.

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Section: A -~-A -~~~L~-a -A -mentioning

confidence: 92%

Comparison of the Secretory Actions of 5-Hydroxytryptamine in the Proximal and Distal Colon of the Rat

Ayton

Hardcastle

et al. 1995

Journal of Pharmacy and Pharmacology

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“…5-HT 3 receptors have been documented in the rat small intestine by a radioligand binding assay, but the exact localization was not studied. 24 They could thus be located in the mucosa or on the enteric neurones. The presence of 5-HT 3 receptors was also demonstrated in a functional study using rat jejunum, where neuronal 5-HT 3 receptors mediated contraction.…”

Section: Discussionmentioning

confidence: 99%

5‐HT receptor types in the rat ileum longitudinal muscle: focus on 5‐HT₂ receptors mediating contraction

Briejer

Mathis²,

Schuurkes

1997

Neurogastroenterology Motil

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The 5-hydroxytryptamine (5-HT) receptor(s) that mediate(s) contraction of the rat ileum longitudinal muscle was studied.5-HT and a-methyl-5-HT equipotently induced contractions, whereas 5-methoxytryptamine and 2-methyl-5-HT (partial agonist) were less potent; this rank order of potency suggests involvement of a 5-HT 2 receptor. Neither tetrodotoxin nor atropine affected the contraction to 5-HT, suggesting a smooth muscle localization of these 5-HT 2 receptors. The presence of either a selective 5-HT 2B (SB 204741), 5-HT 3 (granisetron) or 5-HT 4 (SB 204070) antagonist, slightly affected the contractions to 5-HT. Thus, they were also included in the organ bath solution in all subsequent experiments in order to pharmacologically isolate the main contractile component. Using (if possible) 5-HT 2A receptorselective concentrations, ketanserin, ritanserin, metergoline, spiperone, mianserin, methiothepin, mesulergine, methysergide and cisapride all inhibited the contractions to 5-HT, causing a depression of the curve to 5-HT (i.e. surmountable antagonism was not observed with any of the above agents). Comparison of the affinities of these compounds for the various 5-HT 2 receptor subtypes revealed that the receptor involved in the contractions to 5-HT most closely resembles the 5-HT 2A receptor. However, cinanserin at a concentration expected to inhibit 5-HT 2A receptor-mediated effects, failed to affect the contractions to 5-HT.It is thus concluded that on the longitudinal smooth muscle of the rat ileum, at least a part of the contraction to 5-HT is mediated by 5-HT receptors resembling the 5-HT 2A receptor subtype.

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“…This receptor type is predominantly located on terminals of vagal afferent fibers (8,18,43) and is also found within distinct subpopulations of the brain (7,41). In addition to their role in motility, sensory, and secretory functions (14,43,53), 5-HT 3 receptors also contribute to physiologic inhibition of food intake in a variety of feeding paradigms (1,10,24,29).…”

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confidence: 99%

Serotonin-type 3 receptors mediate intestinal lipid-induced satiation and Fos-like immunoreactivity in the dorsal hindbrain

Savastano¹,

Hayes²,

Covașă³

2007

American Journal of Physiology-Regulatory, Integrative and Comp

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The presence of lipids in the small intestine potently suppresses food intake; however, whether 5-HT 3 receptors play a role in this response has not been directly examined. Therefore, using the selective 5-HT3 receptor antagonist ondansetron, we tested the hypothesis that duodenal infusion of lipid suppresses intake of both sucrose solution and chow through 5-HT3 receptor activation. Rats duodenally infused with 72 and 130 mM Intralipid suppressed 1-h 15% sucrose intake by 33 and 67%, respectively. Suppression of sucrose intake by 72 mM Intralipid was significantly attenuated by ondansetron at all doses tested (0.5, 1.0, 2.0, and 5.0 mg/kg ip), whereas the lowest effective dose of ondansetron to attenuate suppression of intake by 130 mM Intralipid was 1.0 mg/kg. Furthermore, infusion of 130 mM Intralipid suppressed 1-and 4-h chow intake by 35 and 20%, respectively. Ondansetron administered as low as 0.5 mg/kg significantly attenuated 1-h Intralipid-induced suppression of chow intake and completely reversed the suppression by 4 h. Administration of ondansetron alone did not alter sucrose or chow intake compared with vehicle injection at any time. Finally, to test whether Intralipidinduced neuronal activation of the dorsal vagal complex is mediated by 5-HT 3 receptors, Fos-like immunoreactivity (Fos-LI) was quantified in ondansetron-pretreated rats following intestinal lipid infusion. Ondansetron (1 mg/kg) significantly attenuated duodenal intralipidinduced Fos-LI in the dorsal hindbrain. These data support the hypothesis that 5-HT3 receptors mediate both satiation, as well as hindbrain neuronal responses evoked by intestinal lipids. food intake; lipids; intestinal chemoreception IT IS WELL ESTABLISHED THAT nutrients within the duodenal lumen early in a meal play an essential role in producing satiation that occurs with meal ingestion. This is supported by evidence that duodenal infusion of lipids reduce sham food intake (20), whereas intravenous infusion of lipids does not (21), demonstrating that the satiating effect of intraduodenal lipids occurs largely before absorbed lipids enter the blood (19). The predominant hypothesis is that paracrine or endocrine products of intestinal origin, secreted in response to intestinal nutrients, activate vagal afferent fibers leading to inhibition of food intake (11,16,42). The indoleamine serotonin (5-HT) is one such signal. Over 95% of the body's 5-HT is located in the gut, with at least 90% present in enterochromaffin (EC) cells that are scattered in the enteric epithelium from the stomach through the colon (15, 17). The abundance of 5-HT in the gut has made this neuromodulator the focus of numerous studies investigating regulatory feedback mechanisms of food intake.Systemic serotonergic activity regulates gastrointestinal functions through activation of a number of receptors, including the excitatory, ligand-gated cation channel 5-HT type-3 (5-HT 3 ) receptor. This receptor type is predominantly located on terminals of vagal afferent fibers (8,18,43) and is also found wi...

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Identification and distribution of 5‐HT₃ recognition sites in the rat gastrointestinal tract

Cited by 33 publications

References 24 publications

Comparison of the Secretory Actions of 5-Hydroxytryptamine in the Proximal and Distal Colon of the Rat

Comparison of the Secretory Actions of 5-Hydroxytryptamine in the Proximal and Distal Colon of the Rat

5‐HT receptor types in the rat ileum longitudinal muscle: focus on 5‐HT₂ receptors mediating contraction

Serotonin-type 3 receptors mediate intestinal lipid-induced satiation and Fos-like immunoreactivity in the dorsal hindbrain

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Identification and distribution of 5‐HT3 recognition sites in the rat gastrointestinal tract

Cited by 33 publications

References 24 publications

Comparison of the Secretory Actions of 5-Hydroxytryptamine in the Proximal and Distal Colon of the Rat

Comparison of the Secretory Actions of 5-Hydroxytryptamine in the Proximal and Distal Colon of the Rat

5‐HT receptor types in the rat ileum longitudinal muscle: focus on 5‐HT2 receptors mediating contraction

Serotonin-type 3 receptors mediate intestinal lipid-induced satiation and Fos-like immunoreactivity in the dorsal hindbrain

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Identification and distribution of 5‐HT₃ recognition sites in the rat gastrointestinal tract

5‐HT receptor types in the rat ileum longitudinal muscle: focus on 5‐HT₂ receptors mediating contraction