Serotonin type-4 receptors modulate the sensitivity of intramural mechanoreceptive afferents of the cat rectum

It has been suggested that serotonin (5-hydroxytryptamine) type-4 (5-HT (4) ) receptors modulate the sensitivity of intrinsic afferents of the intestinal mucosa. We studied the involvement of 5-HT (4) receptors in the modulation of extrinsic afferent sensitivity of the intestinal wall. During distension ramps, mechanoreceptive rectal afferents in sacral dorsal roots were examined in decerebrate anaesthesia-free cats using the selective 5-HT (4) receptor partial agonist, tegaserod (HTF 919), and the 5-HT (4) receptor antagonist, SB 203186. The static discharge rate of the afferents evoked by rectal distension decreased after intravenous (i.v.) administration of tegaserod at intraluminal pressures above 30 mmHg, with the most effective reduction occurring at 50 mmHg. The effect was dose-dependent, with maximal reduction occurring at 1.2 mg kg (-1) bodyweight, and could be partly reversed by i.v. administration of SB 203186. Tegaserod did not alter the pressure-volume relationship (compliance) of the rectum. It is tentatively concluded that 5-HT (4) receptor activation has an inhibitory effect on intramural mechanoreceptors in the cat's rectum. Our results are in line with the observation that tegaserod relieves the sensory symptoms of patients suffering from irritable bowel syndrome.