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Excitation of rat colonic afferent fibres by 5‐HT 3 receptors
Author(s) -
Hicks Gareth A.,
Coldwell Jonathan R.,
Schindler Marcus,
Ward Philip A. Bland,
Jenkins David,
Lynn Penny A.,
Humphrey Patrick P. A.,
Blackshaw L. Ashley
Publication year - 2002
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2002.025452
Subject(s) - receptor , medicine , 5 ht receptor , agonist , endocrinology , dorsal root ganglion , serotonin , mechanoreceptor , irritable bowel syndrome , anatomy , chemistry , stimulation , dorsum
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.