Exogenous serotonin regulates colorectal motility via the 5-HT2 and 5-HT3 receptors in the spinal cord of rats

Abstract

Background

We previously reported that intrathecal injection of noradrenaline or dopamine causes enhancement of colorectal motility. As these monoamines are neurotransmitters of descending pain inhibitory pathways in the spinal cord, we hypothesized that serotonin, which is one of the neurotransmitters involved in descending pain inhibition, also influences the lumbosacral defecation center. Therefore, we examined whether serotonin acting on the spinal defecation center enhances colorectal motility.

Methods

Colorectal intraluminal pressure and propelled liquid volume were recorded in vivo in anesthetized rats.

Key Results

Intrathecal injection of serotonin into the L6-S1 spinal cord elicited periodic increases in colorectal intraluminal pressure, being associated with increases in liquid output. Pharmacological experiments revealed that the effect of serotonin is mediated by both 5-HT₂ and 5-HT₃ receptors. The serotonin-induced enhancement of colorectal motility was unaffected even after disconnection of the defecation center from supraspinal regions by cutting the T8 spinal cord, while transection of the parasympathetic pelvic nerves prevented the colokinetic effect of serotonin. Finally, we investigated interactions among serotonin, noradrenaline and dopamine. Simultaneous administration of sub-effective doses of these monoamine neurotransmitters into the spinal cord caused propulsive colorectal motility slightly but substantially.

Conclusions and Inferences

These results demonstrate that exogenous serotonin acts on 5-HT₂ and 5-HT₃ receptors in the lumbosacral defecation center and activates the parasympathetic nervous system to enhance colorectal motility in cooperation with noradrenaline and dopamine.

This study demonstrates that serotonin applied into the lumbosacral spinal cord causes enhancement of colorectal motility via the pelvic nerves. In addition, serotonin, noradrenaline and dopamine have interactive effects in the lumbosacral defecation center to promote propulsive contractions of the colorectum. Monoamine receptors in the lumbosacral defecation center represent new potential drug targets against colorectal dysmotility.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vlKx4i