Fig. 3.

Inhibition of 5-HT₃ receptor responses by VUF10166. A, typical 5-HT₃A receptor responses. 5-HT (2 μM) was applied three times at 1-min intervals to show that the response is stable (i), 30 nM VUF10166 reduces the maximal current to ∼50% of its initial value (ii), and the response has a similar amplitude with the next application of 5-HT alone (iii). A further application of 30 nM VUF10166 reduces the current by ∼50% again (iv), and the subsequent 5-HT responses show slow recovery. B, a typical trace showing inhibition and recovery of a 5-HT₃A receptor response with 3 nM VUF10166. First, a stable 2 μM 5-HT response is recorded. Coapplication of 5-HT and VUF10166 reduces the maximal current. Increasing inhibition is observed during subsequent 5-HT applications, and the response slowly recovers when the VUF10166 is removed. These data also show that coapplication reduces the response by 7% (a), which is less than the 14% reduction that is seen when the same concentration of VUF10166 is preapplied (b, c, d, and e). C, at 5-HT₃AB receptors, maximal VUF10166 inhibition reaches a stable level after a 1-min application whether VUF10166 (30 nM) is preapplied (a) or coapplied (b), and recovery is similar. D, at 5-HT₃AB receptors, maximal VUF10166 inhibition is reached after a 1-min application. E, recovery from VUF10166 application was slower at 5-HT₃A than at 5-HT₃AB receptors; 5-HT₃AB receptors recovered from inhibition within 8 min, whereas recovery for 5-HT₃A receptor responses is >25 min. F, a VUF10166 concentration-inhibition curve at 5-HT₃AB receptors. Values are mean ± S.E.M., with sample size and other parameters shown in the text and tables.