title: Serotonin augments gut pacemaker activity via 5-HT3 receptors.
abstract: Serotonin (5-hydroxytryptamine: 5-HT) affects numerous functions in the gut, such as secretion, muscle contraction, and enteric nervous activity, and therefore to clarify details of 5-HT's actions leads to good therapeutic strategies for gut functional disorders. The role of interstitial cells of Cajal (ICC), as pacemaker cells, has been recognised relatively recently. We thus investigated 5-HT actions on ICC pacemaker activity. Muscle preparations with myenteric plexus were isolated from the murine ileum. Spatio-temporal measurements of intracellular Ca(2+) and electric activities in ICC were performed by employing fluorescent Ca(2+) imaging and microelectrode array (MEA) systems, respectively. Dihydropyridine (DHP) Ca(2+) antagonists and tetrodotoxin (TTX) were applied to suppress smooth muscle and nerve activities, respectively. 5-HT significantly enhanced spontaneous Ca(2+) oscillations that are considered to underlie electric pacemaker activity in ICC. LY-278584, a 5-HT(3) receptor antagonist suppressed spontaneous Ca(2+) activity in ICC, while 2-methylserotonin (2-Me-5-HT), a 5-HT(3) receptor agonist, restored it. GR113808, a selective antagonist for 5-HT(4), and O-methyl-5-HT (O-Me-5-HT), a non-selective 5-HT receptor agonist lacking affinity for 5-HT(3) receptors, had little effect on ICC Ca(2+) activity. In MEA measurements of ICC electric activity, 5-HT and 2-Me-5-HT caused excitatory effects. RT-PCR and immunostaining confirmed expression of 5-HT(3) receptors in ICC. The results indicate that 5-HT augments ICC pacemaker activity via 5-HT(3) receptors. ICC appear to be a promising target for treatment of functional motility disorders of the gut, for example, irritable bowel syndrome.
authors.affiliation: Department of Cell Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hong-Nian
authors.initials: HN
authors.lastname: Liu
authors.forename: Susumu
authors.initials: S
authors.lastname: Ohya
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: Kenta
authors.initials: K
authors.lastname: Sawamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Iino
authors.forename: Mohsin Md
authors.initials: MM
authors.lastname: Syed
authors.forename: Kazunori
authors.initials: K
authors.lastname: Goto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Imaizumi
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D007082:Ileum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007124:Immunoenzyme Techniques; D056885:Interstitial Cells of Cajal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009197:Myenteric Plexus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D044406:Receptors, Serotonin, 5-HT3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D044406:Receptors, Serotonin, 5-HT3; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D002118:Calcium