Tonic inhibition of human small intestinal motility by nitric oxide in children but not in adults

Abstract

Background Gastrointestinal motility is dependent on neural influences that largely involve the enteric nervous system (ENS). The main motor patterns that occur in the fasted and fed state are noticeably different in children compared with adults. Although the development of the ENS continues after birth, there is no data on the contractile activity of segments of small intestine from young children. This study was designed to provide data on the development of muscle control by the human ENS with particular attention to acetylcholine (ACh) and nitric oxide (NO) as the primary neurotransmitters of enteric motor neurons, respectively. Methods Small intestinal specimens were obtained from 11 children and six adults undergoing surgery for various diseases. The mechanical activity of the circular muscle was recorded in vitro. The effects of N x -nitro-L-arginine methyl ester hydrochloride, an inhibitor of NO synthesis, and of atropine, an antagonist of muscarinic receptors, were tested on the spontaneous motility and responses to nerve stimulation. Key Results Spontaneous motility was observed in all preparations. Responses to nerve stimulation were identical in child and adult. No tonic cholinergic excitation of small intestinal motility was observed either in child or in adult. Inhibition of NO synthesis induced a major disinhibition of motility in child but not in adult. Conclusions & Inferences Spontaneous intestinal motility and cholinergic and nitrergic neurotransmission are present from birth. NO provides a tonic inhibition of intestinal motility only in child. Our study indicates that NO may be a major player in shaping the ontogenic development of intestinal motility in human.

Nitric oxide in enteric nervous system mediated the inhibitory effect of vasopressin on the contraction of circular muscle strips from colon in male rats

“…Nitric oxide is the primary neurotransmitter of inhibitory motoneurons in ENS 53 and exerts tonic inhibition on intestinal motility in child 54 . In this study, we found that both TTX and l ‐NAME excited CM contraction.…”

Myenteric neurons of the mouse small intestine undergo significant electrophysiological and morphological changes during postnatal development

“…Previous studies of guinea‐pig, rat and human have reported postnatal changes in the proportions of different types of enteric neurons and in enteric neuromuscular transmission (de Vries et al 2010; Patel et al 2010; Wittmeyer et al 2010). Our study, which is the first to examine developmental changes in electrophysiological and morphological properties of neurons in an intact ENS, found that the main neuron types (DII and S‐neurons with a single long process) comprising reflex pathways underlying the propulsive behaviour of the gut could be distinguished by P0.…”

Butyrate enemas enhance both cholinergic and nitrergic phenotype of myenteric neurons and neuromuscular transmission in newborn rat colon

“…In particular, in rat neonates, the proportion of nitrergic myenteric neurons increases early in the postnatal life followed by a significant increase in the proportion of cholinergic neurons (44). In the human and guinea pig small intestine, a stronger nitrergic inhibitory component of the neuromuscular transmission is observed in neonates than in adults (32,46). The maturation of the cholinergic phenotype of myenteric neurons is correlated with the development of colonic migrating motor complexes in mice (37) and colonic propulsive motility in rats (44).…”