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

Abstract

It has been suggested that serotonin (5-hydroxytryptamine) type-4 (5-HT4) receptors modulate the sensitivity of intrinsic afferents of the intestinal mucosa. We studied the involvement of 5-HT4receptors 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-HT4receptor partial agonist, tegaserod (HTF 919), and the 5-HT4receptor 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-HT4receptor 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.

Dai-Kenchu-To, a Herbal Medicine, Attenuates Colorectal Distention-induced Visceromotor Responses in Rats

“…24 5-HT 4 receptor agonists and CGRP have also been suggested to have antinociceptive properties. [10][11][12] Tegaserod, a 5-HT 4 agonist, increased the pain threshold of awake rats subjected to colorectal distention without modifying rectal compliance. 12 Therefore, together with these results, the effect of DKT, which attenuates colorectal distention-induced VMRs, may be mediated through the action of the 5-HT 4 receptor and/or CRD, colorectal distention; ACTH, adrenocorticotropic hormone; DKT, Dai-kenchu-to.…”

“…Visceromotor responses were analyzed using electromyography in response to colorectal distention (10,20, 40, 60, and 80 mmHg for 20 seconds at 3-minutes intervals). Anxiety-related behavior was measured during exposure to an elevated-plus maze after colorectal distention.…”

“…For the control group, the colon was then distended with 10 mmHg intensity stimulations for 1000 seconds. For the vehicletreated and DKT-treated groups, the colon was distended with graded (10,20,40,60, and 80 mmHg colorectal distention) intensity stimulations for 20 seconds per stimulation, with an interval of 3 minutes between stimuli.…”

“…A 5-HT 4 agonist and CGRP stimulated gastrointestinal motility, 8,9 whereas the same 5-HT 4 agonist and CGRP suppressed colorectal distention-induced visceromotor responses. [10][11][12] Colorectal distention is widely used as a model for visceral stimulation. It is generally accepted that 80 mmHg of colorectal distention is a noxious stimulus; this pressure is perceived as painful by human beings 13 and considered noxious in rats.…”

Analgesic activity of cynaropicrinon on post‑inflammatory irritable bowel syndrome visceral hypersensitivity in a rat model

“…These findings suggest that altered EC cells or 5-HT might be one pathophysiologic mechanism contributing to visceral pain in PI-IBS. More than 90% of 5-HT in the body is secreted from EC cells which are located within the mucosal mucosa, and the tryptophan hydroxylase (TPH) which in EC cells is the rate-limiting enzyme in the 5-HT synthesis process (5)(6)(7). Moreover, recent studies indicated that CD4 + T cells played an important role in the development of colonic EC cell hyperplasia in intestinal infection, and EC cells were influenced by helper T-cell subtype 1 (Th1) or subtype 2 (Th2) cytokine predominant environments (8,9).…”