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10:04
Whole Cell Electrophysiology of Primary Cultured Murine Enterochromaffin Cells
Published on: September 26, 2018
Serotonin augments gut pacemaker activity via 5-HT3 receptors
Hong-Nian Liu1, Susumu Ohya, Yuji Nishizawa
1Department of Cell Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Plos One
|September 28, 2011
Summary
Serotonin (5-HT) enhances interstitial cells of Cajal (ICC) pacemaker activity through 5-HT(3) receptors. This finding suggests ICC are a potential therapeutic target for gut motility disorders.
Area of Science:
- Gastroenterology
- Neurogastroenterology
- Cell Physiology
Background:
- Serotonin (5-hydroxytryptamine: 5-HT) plays a crucial role in regulating gut functions, including secretion and motility.
- Interstitial cells of Cajal (ICC) are recognized as the primary pacemaker cells responsible for initiating gut motility.
- Understanding 5-HT's influence on ICC is vital for developing treatments for functional gastrointestinal disorders.
Purpose of the Study:
- To investigate the specific actions of serotonin (5-HT) on the pacemaker activity of interstitial cells of Cajal (ICC).
- To elucidate the receptor subtypes involved in mediating 5-HT's effects on ICC.
- To explore the potential of ICC as a therapeutic target for functional gut disorders.
Main Methods:
- Isolated murine ileum preparations with myenteric plexus were used.
- Spatio-temporal intracellular Ca(2+) imaging and microelectrode array (MEA) systems were employed to measure ICC activity.
- Pharmacological agents including 5-HT receptor antagonists (LY-278584, GR113808) and agonists (2-Me-5-HT, O-Me-5-HT), along with smooth muscle (DHP) and nerve (TTX) suppressors, were utilized.
Main Results:
- Serotonin (5-HT) significantly enhanced spontaneous Ca(2+) oscillations and electrical activity in ICC.
- The 5-HT(3) receptor antagonist LY-278584 suppressed ICC activity, while the agonist 2-Me-5-HT restored it, indicating a role for 5-HT(3) receptors.
- Selective 5-HT(4) antagonists and non-selective agonists showed minimal effects, further implicating 5-HT(3) receptors.
- RT-PCR and immunostaining confirmed the expression of 5-HT(3) receptors in ICC.
Conclusions:
- Serotonin (5-HT) augments ICC pacemaker activity predominantly through the activation of 5-HT(3) receptors.
- These findings highlight interstitial cells of Cajal (ICC) as a promising cellular target for therapeutic interventions in functional gut motility disorders, such as irritable bowel syndrome.
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