Evidence for a 5‐HT 3 receptor involvement in the facilitation of peristalsis on mucosal application of 5‐HT in the guinea pig isolated ileum

1 The 5‐HT receptor involved in the effect of mucosal application of 5‐HT to facilitate peristalsis was investigated in the isolated guinea pig ileum. 2 An application of 5‐HT (3–100 μ M ) to the mucosal surface (by inclusion of 5‐HT in the Krebs‐Henseleit solution passing through the lumen of the ileum) caused a concentration related facilitation of peristalsis characterized by a reduction in the peristaltic threshold. 3 Peristalsis was not modified by methiothepine (0.1 μ M ), ritanserin (0.1 μ M ), ondansetron (5 μ M ), granisetron (1 μ M ) or SB 204070 (0.1 μ M ) administered alone to the mucosal surface. 4 The concentration–response curve to mucosally applied 5‐HT was not altered by the mucosally applied 5‐HT 1/2 receptor antagonist methiothepine (0.1 μ M ), the 5‐HT 2 receptor antagonist ritanserin (0.1 μ M ) or the 5‐HT 4 receptor antagonist SB 204070 (0.1 μ M ). However, the mucosally applied 5‐HT 3 receptor antagonists ondansetron (5 μ M ) and granisetron (1 μ M ) shifted the response curves to mucosally applied 5‐HT to the right in a parallel and surmountable manner. The pD 2 values in the absence and presence of ondansetron were 5.42±0.07 and 4.12±0.10, respectively, ( n =6) and that of granisetron were 5.45±0.12 and 4.50±0.10 respectively, ( n =5). 5 Serosally applied ondansetron (5 μ M ) or granisetron (1 μ M ) had no effect on the concentration–response curve to mucosally applied 5‐HT. However, the serosally applied ondansetron and granisetron antagonised the facilitatory effect of serosally applied 5‐HT (10 μ M ) when administered in the presence of serosally applied SB 204070 (0.1 μ M ). 6 It is concluded that the facilitatory effect of mucosally applied 5‐HT to reduce the peristaltic threshold in the guinea pig ileum is mediated via a 5‐HT 3 receptor located on the mucosal and not the serosal side of the ileum.British Journal of Pharmacology (1997) 122 , 1174–1178; doi: 10.1038/sj.bjp.0701503