• 5-HT4 receptors;
  • relaxation;
  • 5-hydroxytryptamine;
  • canine;
  • rectum;
  • colon;
  • large intestine
  • This study aimed to characterize for the first time in vitro 5-HT4 receptors in the canine gastrointestinal tract. For this purpose, we used circular muscle strips of the canine isolated rectum.

  • In the presence of methysergide (60 μM), 5-HT induced relaxation of methacholine (1 μM)-precontracted muscle strips, yielding a monophasic sigmoidal concentration-relaxation curve (pEC50 7.2±0.07).

  • Tetrodotoxin (0.3 μM) did not affect the curve to 5-HT, suggesting the inhibitory 5-HT receptor is located on the smooth muscle. Granisetron (0.3 μM) did also not affect the curve to 5-HT, which excludes the 5-HT3 receptor mediating the relaxation to 5-HT. The presence of methysergide rules out the involvement of 5-HT1, 5-HT2 or 5-HT7 receptors.

  • 5-HT, the selective 5-HT4 receptor agonists R076186, prucalopride (R093877) and SDZ HTF-919 and the 5-HT4 receptor agonists cisapride and 5-MeOT relaxed the muscle strips with a rank order of potency R076186=5-HT>cisapride>prucalopridegeqslant R: gt-or-equal, slantedSDZ HTF-919>5-MeOT.

  • The selective 5-HT4 receptor antagonists GR 125487, RS 39604 and GR 113808 competitively antagonized the relaxations to 5-HT, yielding pKB estimates of 9.7, 7.9 and 9.1, respectively. The selective 5-HT4 receptor antagonist SB 204070 shifted the curve to 5-HT rightward and depressed the maximal response (apparent pA2 10.6). GR 113808 (10 nM) produced a parallel rightward shift of the curve to the selective 5-HT4 receptor agonists R076186 (pA2 8.8).

  • It is concluded that 5-HT induces relaxation of the canine rectum circular muscle through stimulation of a single population of smooth muscle 5-HT4 receptors. For the first time, a non-human species was shown to exhibit relaxant 5-HT4 receptors in the large intestine.

British Journal of Pharmacology (1999) 127, 1431–1437; doi:10.1038/sj.bjp.0702665