Activation of 5‐HT 3 receptors in the rat and mouse intestinal tract: a comparative study

1 This study provides a comprehensive evaluation of 5‐HT 3 receptor functional distribution in both the rat and mouse intestinal tract. 2 5‐HT 3A−S receptor splice variant mRNA was expressed throughout the intestine of the rat and mouse; the 5‐HT 3A−L variant being more common in the rat. 3 5‐HT, m‐CPB, 1‐PBG and 2‐methyl‐5‐hydroxytryptamine (2m5‐HT) induced contraction in the jejunum, ileum, proximal colon and distal colon of the rat (pEC 50 range: 2m5‐HT, 5.86±0.40 to m‐CPB, 7.47±0.27) and mouse (pEC 50 range: 1‐PBG, 5.34±0.06 to m‐CPB, 6.49±0.14) in the presence of nontarget 5‐HT receptor antagonists, methysergide (1  μ M ) and GR125487 (0.1  μ M ). The rank orders of potency in the four regions of the rat and mouse intestine were concordant with the accepted order and the responses to 5‐HT were inhibited by ondansetron (0.1  μ M ). 4 5‐HT 3 ‐induced contractions to 5‐HT were reduced by tetrodotoxin (1  μ M ). Pargyline (10  μ M ) and fluoxetine (1  μ M ) potentiated responses in the rat jejunum. Atropine (0.1  μ M ) potentiated 5‐HT 3 ‐induced responses in the rat jejunum ( E max 49–65%), but attenuated responses in most other regions of the rat and mouse (e.g. mouse ileum: E max 57–26%). In the rat jejunum, L ‐NAME (100  μ M ) mimicked the effect of atropine, hexamethonium (100  μ M ) suppressed 5‐HT 3 ‐induced responses, but tachykinin receptor antagonists were without effect. 5 It is concluded that functional 5‐HT 3 receptors are present in nerves along the length of the rat and mouse intestinal tract. The mouse proximal colon was found to discriminate 5‐HT 3 receptor agonist profiles better than any other region in the rat or mouse. The rat jejunum shows evidence of 5‐HT uptake and inactivation processes as well as inhibitory nitrergic and nontachykinin excitatory pathways associated with the 5‐HT 3 ‐induced response.British Journal of Pharmacology (2006) 148 , 1012–1021. doi: 10.1038/sj.bjp.0706802