5-HT-RECEPTOR SUBTYPES INVOLVED IN THE STIMULATORY EFFECT OF 5-HT ON THE PERISTALTIC REFLEX INVITRO

The effect of serotonin (5-HT) and of more selective 5-HT agonists on the peristaltic reflex evoked in the isolated guinea-pig ileum was inv estigated. Using the Trendelenburg technique, peristaltic contractions were elicited by increasing intraluminal pressure, and rhythmic contr actions of the longitudinal and circular muscle were measured after se rosal administration of the drugs. 5-HT potently stimulated contractio ns of the longitudinal muscle. The effect of 5-HT was partly antagoniz ed by the 5-HT4 receptor antagonist SDZ 205-557. Of the potent 5-HT1A receptor agonists, 8-OH-DPAT, 5-carboxamidotryptamine (5-CT) and dipro pyl-5-CT (DP-5-CT), only 5-CT caused a substantial stimulation. Of the 5-HT1C-/5-HT2 receptor agonists DOI and 5-methoxytryptamine (5-MeOT), DOI was inactive, whereas 5-MeOT potently stimulated contractions. 5- HT1D receptor agonists (5-CT1 sumatriptan) had a stimulatory effect. T he effect of sumatriptan was antagonized by the 5-HT1D receptor antago nist metitepine but not by the 5-HT4 receptor antagonist SDZ 205-557. The 5-HT3 receptor agonist 2-methyl-5-HT and the antagonists ICS 205-9 30 and granisetron did not influence the peristaltic reflex. 6-OH-inda lpine, a 5-HT1P agonist, was inactive. This data suggest that 5-HT sti mulates the peristaltic reflex in the isolated guinea-pig ileum by act ivation of 5-HT4- and 5-HT1D receptors; other 5-HT receptor subtypes a ppear not to play a significant role in the modulation of this reflex.