Intestinal infusions of oleate and glucose activate distinct enteric neurons in the rat

Nutrients entering the small intestine trigger a variety of neural and endocrine reflexes that involve specific afferents, efferents and interneurons, many of which are located within the enteric nervous system (ENS). We hypothesized that intestinal nutrient stimuli might activate specific subpopulations of these neurons. To test this hypothesis, we utilized immunohistochemical detection of nuclear c-fos expression in the myenteric and submucosal plexuses of the rat small intestine following intraintestinal infusions of oleate or glucose. Additionally, we used dual label methods to detect both Fos-immunoreactivity and immunoreactivity for five phenotypic neuronal markers: neurokinin-1 receptor (NK-1R), neurofilament-M (NF-M), neuronal nitric oxide synthase (NOS), calbindin (Cal) and calretinin (Calr), to characterize neurons that were activated by intestinal infusion of oleate and glucose. We found that oleate and glucose activated myenteric neurons in the duodenum and jejunum, but not the ileum. Oleate and glucose infusions significantly increased the number of Fos-immunoreactive nuclei in the submucosal plexus of the duodenum and jejunum, however, only glucose increased Fos-immunoreactivity in the ileum. Oleate and glucose infusions were associated with a small increase in Fos-immunoreactivity in NOS-immunoreactive neurons in the myenteric plexus. In the submucosal plexus, the majority of neurons activated by intestinal infusion of oleate or glucose were immunoreactive to Cal and Calr. In the rat, many of these neurons have Dogiel Type II-like morphology, which is consistent with the possibility that these neurons function as mucosal afferents in reflexes activated by nutrient stimuli.