Nitric oxide synthase immunoreactivity in the enteric nervous system of the developing human digestive tract

Abstract

We have investigated indirectly the presence of nitric oxide in the enteric nervous system of the digestive tract of human fetuses and newborns by nitric oxide synthase (NOS) immunocytochemistry and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry. In the stomach, NOS immunoactivity was confined to the myenteric plexus and nerve fibres in the outer smooth musculature; few immunoreactive nerve cell bodies were found in ganglia of the outer submucous plexus. In the pyloric region, a few nitrergic perikarya were seen in the inner submucous plexus and some immunoreactive fibers were found in the muscularis mucosae. In the small intestine, nitrergic neurons clustered just underneath or above the topographical plane formed by the primary nerve strands of the myenteric plexus up to the 26th week of gestation, after which stage, they occurred throughout the ganglia. Many of their processes contributed to the dense fine-meshed tertiary nerve network of the myenteric plexus and the circular smooth muscle layer. NOS-immunoreactive fibres directed to the circular smooth muscle layer originated from a few NOS-containing perikarya located in the outer submucous plexus. In the colon, caecum and rectum, labelled nerve cells and fibres were numerous in the myenteric plexus; they were also found in the outer submucous plexus. The circular muscle layer had a much denser NOS-immunoreactive innervation than the longitudinally oriented taenia. The marked morphological differences observed between nitrergic neurons within the developing human gastrointestinal tract, together with the typical innervation pattern in the ganglionic and aganglionic nerve networks, support the existence of distinct subpopulations of NOS-containing enterice neurons acting as interneurons or (inhibitory) motor neurons.

The effects of endogenous and exogenous nitric oxide on gut motility in zebrafish Danio rerio embryos and larvae

“…Similar results have been reported from studies in prenatal mammals (Timmermans et al, 1994;Brandt et al, 1996; van Ginneken . The effects of L-NAME and SNP on isolated strip preparations from adult zebrafish.…”

“…A variety of neurotransmitters have been identified in the developing gut in mammals (Gintzler et al, 1980;Rothman and Gershon, 1982;Larsson et al, 1987;Timmermans et al, 1994;Brandt et al, 1996;van Ginneken et al, 1998), birds (Epstein et al, 1985;Rothman et al, 1986;Balaskas et al, 1995), amphibians (Holmberg et al, 2001;Maake et al, 2001;Badawy and Reinecke, 2003) and teleosts (Reinecke et al, 1997;Villani, 1999;Poon et al, 2003;Holmberg et al, 2004;Holmqvist et al, 2004;Pederzoli et al, 2004). In the zebrafish, enteric neurons are present in the gut before the onset of exogenous feeding (Raible et al, 1992;Bisgrove et al, 1997;Holmberg et al, 2003).…”

Fetal Intestinal Obstruction Induces Alteration of Enteric Nervous System Development in Human Intestinal Atresia

“…Progressive maturation of ENS was further evidenced using antibody recognizing an epitope common to the three subnunits of the cytoskeletal neuronal protein NF and nNOS, a nonadrenergic noncholinergic mediator of the nervous system produced by enteric neurons with inhibitory functions (14,15). The latter protein plays a key role in the regulation of intestinal motility (16,17). Both markers had a similar pattern of expression during development, being first detected at the beginning of the second trimester.…”

Role of enteric glial cells in inflammatory bowel disease

“…Thirdly, EGCs have recently been shown to be the only cells within the ENS that are immunoreactive for L-arginine (Nagahama et al, 2001), a substrate required for the nitric oxide (NO) synthesis. NO is a mediator of intercellular signaling and is considered an important neurotransmitter in the ENS since NO synthase (NOS) immunoreactive neurons account for 20%-30% of ENS neurons Llewellyn-Smith et al, 1992;Ekblad et al, 1994;Timmermans et al, 1994). Therefore, EGCs may represent a major source of L-arginine in the ENS, transferring it to neurons when required.…”