In:
The Journal of Physiology, Wiley, Vol. 544, No. 3 ( 2002-11), p. 861-869
Abstract:
The gastrointestinal tract contains most of the body's 5‐hydroxytryptamine (5‐HT) and releases large amounts after meals or exposure to toxins. Increased 5‐HT release occurs in patients with irritable bowel syndrome (IBS) and their peak plasma 5‐HT levels correlate with pain episodes. 5‐HT 3 receptor antagonists reduce symptoms of IBS clinically, but their site of action is unclear and the potential for other therapeutic targets is unexplored. Here we investigated effects of 5‐HT on sensory afferents from the colon and the expression of 5‐HT 3 receptors on their cell bodies in the dorsal root ganglia (DRG). Distal colon, inferior mesenteric ganglion and the lumbar splanchnic nerve bundle (LSN) were placed in a specialized organ bath. Eighty‐six single fibres were recorded from the LSN. Three classes of primary afferents were found: 70 high‐threshold serosal afferents, four low‐threshold muscular afferents and 12 mucosal afferents. Afferent cell bodies were retrogradely labelled from the distal colon to the lumbar DRG, where they were processed for 5‐HT 3 receptor‐like immunoreactivity. Fifty‐six percent of colonic afferents responded to 5‐HT (between 10 −6 and 10 −3 M) and 30 % responded to the selective 5‐HT 3 agonist, 2‐methyl‐5‐HT (between 10 −6 and 10 −2 M). Responses to 2‐methyl‐5‐HT were blocked by the 5‐HT 3 receptor antagonist alosetron (2 × 10 −7 M), whereas responses to 5‐HT were only partly inhibited. Twenty‐six percent of L1 DRG cell bodies retrogradely labelled from the colon displayed 5‐HT 3 receptor‐like immunoreactivity. We conclude that colonic sensory neurones expressing 5‐HT 3 receptors also functionally express the receptors at their peripheral endings. Our data reveal actions of 5‐HT on colonic afferent endings via both 5‐HT 3 and non‐5‐HT 3 receptors.
Type of Medium:
Online Resource
ISSN:
0022-3751
,
1469-7793
DOI:
10.1113/jphysiol.2002.025452
Language:
English
Publisher:
Wiley
Publication Date:
2002
detail.hit.zdb_id:
1475290-6
SSG:
12
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