EVIDENCE FOR A 5-HT3 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 peristalis was investigated in the isolated guinea p ig. 2 An application of 5-HT (3-100 mu) to the mucosal surface (by inc lusion of 5-HT in the Krebs-Henseleit solution passing through the lum en of the ileum) caused a concentration related facilitation of perist alsis characterized by a reduction in the peristaltic threshold. 3 Per istalsis was not modified by methiothepine (0.1 mu M), ritanserin (0.1 mu M), ondantsetron (5 mu M), granisetron (1 mu M) or SB 204070 (0.1 mu M) administered alone to the mucosal surface. 4 The concentration-r esponse curve to mucosally applied 5-HT was not altered by the mucosal ly applied 5-HT1/2 receptor antagonist methiothepine (0.1 mu M), the 5 -HT2 receptor antagonist ritanserin (0.1 mu M) or the 5-HT4 receptor a ntagonist SB 204070 (0.1 mu M). However, the mucosally applied 5-HT3 r eceptor antagonists ondansetron (5 mu M) and granisetron (1 mu M) shif ted the response curve to mucosally applied 5-HT to the right in a par allel and surmountable manner. The pD(2) values in the absence and pre sence of ondansetron were 5.42 +/- 0.07 and 4.12 +/- 0.10, respectivel y, (n = 6) and that of granisetron were 5.45 +/- 0.12 and 4.50 +/- 0.1 0 respectively, (n = 5). 5 Serosally applied ondansetron (5 mu M) or g ranisetron (1 mu 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 appli ed 5-HT (10 mu M) when administered in the presence of serosally appli ed SB 204070 (0.1 mu M). 6 It is concluded that the facilitatory effec t of mucosally applied 5-HT to reduce the peristaltic threshold in the guinea pig ileum is mediated via a 5-HT3 receptor located on the muco sal and not the serosal side of the ileum.