Pharmacological characterization of the 5‐HT receptor‐mediated contraction in the mouse isolated ileum

• Published in: British journal of pharmacology Vol. 131; no. 8; pp. 1716 - 1722
• Main Authors: Tuladhar, B R, Womack, M D, Naylor, R J
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-12-2000; Nature Publishing
• Subjects: 5‐HT3 receptor; 5‐hydroxytryptamine; Animals; Atropine - pharmacology; Biological and medical sciences; Cell receptors; Cell structures and functions; Dioxanes - pharmacology; Dose-Response Relationship, Drug; Female; Fundamental and applied biological sciences. Psychology; granisetron; Granisetron - pharmacology; Ileum - drug effects; Ileum - physiology; In Vitro Techniques; Indoles - pharmacology; Intestine. Mesentery; Ketanserin - pharmacology; Male; MDL 72222, m‐chlorophenylbiguanide, 2‐methyl‐5‐hydroxytryptamine; Mice; Molecular and cellular biology; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); mouse ileum; Muscle Contraction - drug effects; Muscle Contraction - physiology; ondansetron; Ondansetron - pharmacology; Piperidines - pharmacology; Receptors, Serotonin - drug effects; Receptors, Serotonin - physiology; Ritanserin - pharmacology; Serotonin - pharmacology; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology; tetrodotoxin; Tetrodotoxin - pharmacology; Tropanes - pharmacology; tropisetron; Vertebrates: digestive system; Digestive system; Interspecific comparison; Rodentia; Gut; Smooth muscle; Muscle contraction; Ileum; In vitro; Biological activity; Vertebrata; Mammalia; Guinea pig; Mouse; Animal; 5-HT3 Serotonine receptor; Localization
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0703747

The pharmacological characterization of a 5‐HT receptor‐mediated contractile response in the mouse isolated ileum is described.
In the presence of methysergide (1 μM), 5‐hydroxytryptamine (5‐HT, 0.3–100 μM) produced phasic concentration‐dependent contractions of segments of the mouse isolated ileum with a pEC50 value of 5.47±0.09.
The 5‐HT3 receptor selective agonists m‐chlorophenylbiguanide (0.3–100 μM, pEC50 5.81±0.04), 1‐phenylbiguanide (3–100 μM, pEC50 5.05±0.06) and 2‐methyl‐5‐HT (3–100 μM, pEC50 5.00±0.07) acted as full agonists to induce contractile responses. 5‐methoxytryptamine (0.1–100 μM), RS 67506 (0.1–100 μM) and α‐methyl‐5‐HT (0.1–100 μM) failed to mimic the 5‐HT responses.
The contractile response to 5‐HT was not antagonized by either 5‐HT2 receptor antagonists ritanserin (0.1 μM) or ketanserin (1 μM) nor the 5‐HT4 receptor antagonist SB 204070 (0.1 μM).
The 5‐HT3 receptor selective antagonists granisetron (0.3–1 nM), tropisetron (1–10 nM), ondansetron (10 nM–1 μM) and MDL 72222 (10 nM–1 μM) caused rightward displacement of the concentration‐response curves to 5‐HT. The lower concentrations of the antagonists caused approximate parallel rightward shifts of the concentration‐response curves to 5‐HT with apparent pKB values for granisetron (9.70±0.39), tropisetron (9.18±0.20), ondansetron (8.84±0.24) and MDL 72222 (8.65±0.35). But higher concentrations of antagonists resulted in a progressive reduction in the maximum responses.
The contractile response to 5‐HT was abolished by tetrodotoxin (0.3 μM); atropine (0.1 and 1 μM) decreased the maximum response of the 5‐HT concentration‐response curve by approximately 65%.
It is concluded that a neuronally located 5‐HT3 receptor mediates a contractile response to 5‐HT in the mouse ileum. The 5‐HT3 receptor in the mouse ileum has a different pharmacological profile to that reported for the guinea‐pig ileum.
British Journal of Pharmacology (2000) 131, 1716–1722; doi:10.1038/sj.bjp.0703747