| The enteric nervous system (ENS) regulates multiple functions in the gastrointestinal tract. Within this intricate network, growing evidence suggests that, enteric glia play a vital role in the gut. However, their precise function and inherent signaling mechanisms are poorly characterized. In this thesis, specific mechanisms are revealed in an effort to further characterize these enigmatic cells.;Structural and functional similarities of glia of the central and enteric nervous systems exist, reinforcing the conceivable potential for glial involvement in active signaling within the GI tract. Data characterize various well-described neuroligands and their effects on calcium signaling events within enteric glia---a phenomenon in the brain wherein lies the means to modulate neuronal activity and synaptic transmission. These cells within the intestine have unique signaling characteristics, without which enteric neurons, the gastrointestinal tract, and the organism as a whole would be incapable of survival.;An investigation of the actions of novel lipid compounds in the ENS is revealed. This series of studies was conducted with the long-range goal of understanding information transfer within the GI tract. Enteric glia, and NOT enteric neurons, are found to selectively respond to a family of recently described bioactive lipids including sphingosine-1-phosphate (S1P), a sphingomyelin metabolite, and a related lipid lysophosphatidic acid (LPA). Both molecules are shown to induce Ca2+ signaling in these cells, and their signaling mechanisms characterized on the cellular level, including a depiction of specific involvement with a novel family of G-protein coupled receptors---EDG receptors. Emerging data are also revealed, serving as the foundation for future endeavors, depicting two other new bioactive lipid family members (sphingosylphosphorylcholine and lysophatidylcholine) that similarly appear to serve as signaling molecules in the GI tract with robust calcium responses, further adding to the complexity with which these cells function. Lastly, S1P and related lipids affect cellular behavior at the transcriptional level: inducing expression of early response genes in a model glial cell line.;The work presented here strongly supports a potential role for glia in information transfer within the walls of the bowel and beyond as we demonstrate the increasing diversity of signaling events displayed by these cells. |
