Immunopositive GABAergic neural sites display nitric oxide synthase-related NADPH diaphorase activity in the human colon.

In the enteric nervous system, gamma-aminobutyric acid (GABA) is a transmitter of interneurons which are proposed to innervate excitatory and inhibitory motor neurons. Nitric oxide (NO) is a putative transmitter of enteric inhibitory motor nerves targeted by GABA. In addition, NO is synthesized by a variety of enteric nerves throughout the gut wall indicative of its potential to be a transmitter of other nerve types, including interneurons. We sought to determine if some populations of nitrergic neurons are interneurons in human infant colon. As enteric neural GABA is exclusive to interneurons, colocalization with NO synthase-related NADPH diaphorase was examined. GABA-transaminase (GABA-T) immunohistochemistry was used to identify GABAergic neurons and a histochemical protocol was used as a marker of neuronal NO synthase-related NADPH diaphorase activity in enteric layers. GABA-T immunoreactive neurons were seen in the ganglionated nerve networks of the myenteric and submucosal layers. GABA-T immunoreactive fibres were also present in the longitudinal and circular muscle layers. A subpopulation of GABA-T immunoreactive neurons within both the myenteric and submucosal ganglia express NO synthase-related activity. This colocalization extends further to a subpopulation of fibers within the muscle layers. These findings strongly suggest that in addition to its role in inhibitory motor neurons, NO may also be a transmitter of enteric interneurons.