Involvement of 5‐HT3 and 5‐HT4 receptors in the motor activity of isolated vascularly perfused rat duodenum

Abstract

The involvement of serotonin (5-HT) receptor subtypes in motor activity of the ex vivo vascularly perfused rat duodenum was investigated. Clusters of phasic contractions (CPCs), migrating in an oral to anal direction, were obtained without any stimulation. Drug effects were evaluated by changes in different components of the pressure waves, such as motor index (MI), frequency, amplitude and duration of the CPC. The effect of 5-HT depletion on motor activity was examined in animals treated with p-chlorophenylalanine (PCPA). The MI, frequency and duration of CPC were decreased by PCPA, but the amplitude was not affected, suggesting that endogenous 5-HT may play an important role in regulation of the motor activity of the rat intestine. The importance of the 5-HT receptor subtypes in the regulation of motor activity was examined. Neither the nonselective 5-HT1 and 5-HT2 receptor antagonist, methysergide, nor the 5-HT2 receptor antagonist, ketanserin, affected motor activity. However, the 5-HT3 receptor antagonists, granisetron and azasetron, decreased percentage MI, frequency, percentage amplitude and percentage duration of CPC. The 5-HT4 receptor antagonist, SB204070, exerted both excitatory and inhibitory actions, with a higher dose (10 nM) stimulating percentage MI, frequency, percentage amplitude and percentage duration, and a lower dose (0.1 nM or 1 nM) decreasing percentage MI and percentage duration of CPC. These results suggest that endogenous 5-HT regulates the motor activity of the rat duodenum through 5-HT3 and 5-HT4 receptors, with the former mediating the stimulatory influence and the latter mediating both stimulatory and inhibitory influences.

Strain‐specific genetics, anatomy and function of enteric neural serotonergic pathways in inbred mice

“…In the present study, 5‐HT 3 and 5‐HT 4 antagonists varied in their ability to inhibit jejunal PCCs depending on strain (Table 4); C57Bl/6 jejunum showed a consistently greater sensitivity to 5‐HT 3 and 5‐HT 4 antagonism than Balb/c jejunum. These data in C57Bl/6 jejunum are in broad agreement with the existing literature concerning 5‐HT 3 and 5‐HT 4 receptor‐mediated effects on PCC‐like activity and transit in the small intestine (Brown et al 1993; Nagakura et al 1996; Yamamoto et al 1999; Bush et al 2001). The insensitivity of Balb/c jejunum to the antagonists correlated with the reduced anatomical connectivity of jejunal 5‐HT neurones in this strain.…”

“…The term ‘propagating contractile complexes’ (PCCs) is preferred here, to avoid prejudging the functional relationship between in vitro and in vivo phenomena. Evidence also suggests that 5‐HT 4 receptors may also be involved in control of propulsive activity in the small (Nagakura et al 1997) and large (Kadowaki et al 1996; Yamamoto et al 1999) intestine in vivo . Enteric neurones that label for 5‐HT are highly conserved between species (Costa et al 1982; Barbiers et al 1995; Sang et al 1997; Anlauf et al 2003), suggesting their role is fundamental.…”

A Pilot Study on Duodenal Acid Exposure and Its Relationship to Symptoms in Functional Dyspepsia with Prominent Nausea

“…Previous studies suggested involvement of 5-HT 3 on vagal afferents in mediating the responses to acid (14)(15)(16)(17)(18)(19)(20). In the present study, 5-HT 3 receptor antagonism did not affect duodenal acid exposure after brief acid infusion, suggesting that 5-HT 3 receptors are unlikely to play a key role in the duodenal motor response to acid in man.…”

“…In addition, the mechanisms underlying duodenal motor and sensory responses to acid are poorly understood. Animal studies have shown that acid in the duodenum releases 5-hydroxytrytamine (HT) from enterochromaffin cells in the duodenal mucosa and this, in turn, may activate 5-HT 3 receptors, which are involved in vagal mucosal chemo-sensitive afferents and motor stimulating pathways (14)(15)(16)(17)(18). Furthermore, the 5-HT 3 receptor antagonist ondansetron was shown to reduce the sensation of nausea during gastric distension and intraduodenal lipid infusion in man, probably by acting at duodenal vagal afferents (19,20).…”

The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

“…In the small intestine, 5-HT 4 receptors mediate mucosal secretion and smooth muscle relaxation (41,42). Furthermore, the 5-HT 4 receptor has an established role in mediating contraction responses via a cholinergic mechanism in the guinea-pig intestine and colon (14,43). In the present study, the lack of evidence for the involvement of 5-HT 4 receptors in mediating a response to EFS could be that the receptors do not play a dominant role in mediating a response to endogenously-released 5-HT under normal physiological conditions.…”