Enteric glial cells play a role in neuronal signalling and in inflammation in the gastrointestinal tract
Date
2007
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Abstract
The functions of glial cells in the enteric nervous system remain poorly understood. We hypothesized that enteric glia play a role in enteric neurotransmission and in intestinal inflammation. Enteric glia may participate in neurotransmission as we observed that these cells expressed receptors for neurotransmitters, such as the metabotropic glutamate receptors (mGluR) 2/3 and 5, the a2a-adrenergic receptor and the somatostatin 2A (SSTR2A) receptor. Glial receptor expression was altered during colitis. We observed a redistribution in mGluR immunoreactivity in both trinitrobenzene sulphonic acid (TNBS) colitis in guinea pigs and dextran sodium sulphate (OSS) colitis in mice, while mGluR expression was decreased in the inflamed colons of interleukin-10 gene-deficient (I L-10-1-) mice. SSTR2A immunoreactivity was redistributed in mice given DSS but unchanged in IL-10-1- mice. No changes to enteric ganglia or glial fibrillary acidic protein expression were observed in DSS and IL-10_,_ mice. Stimulation of glial mGluR5 receptors increased the expression of the early immediate gene product, Fos, as well as the phosphorylated form of the extracellular signal-regulated kinase 1/2 (pERK1/2), but did not alter intracellular calcium, demonstrating that glial receptors were functionally activated. Studies in cultured enteric glia proved inconclusive, as their phenotype no longer resembled that in situ. The gliotoxin fluorocitrate specifically stimulated pERK1/2 expression in enteric glia and reduced ilea! motility in vitro and gastrointestinal transit in vivo. No changes in colonic transit or ion transport were observed, nor were there any signs of inflammation, suggesting that glia modulate the enteric neural circuits underlying gastrointestinal motility. Enteric glia of the mouse colon constitutively expressed the inducible nitric oxide synthase, likely due to "physiological" inflammation. The nitric oxide precursor, L-arginine was localized to neurons and glia in the mouse, suggesting that glial cells were not the sole source of L-arginine. No changes in gut transit or in the distribution of glial and neuronal markers were observed in mice deficient for the inducible L-arginine transporter. Taken together, these data demonstrate that enteric glia play a role in enteric neurotransmission, particularly in gastrointestinal motility and that changes in glial receptor expression are a feature of colitis.
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Bibliography: p. 278-351
Some pages are in colour.
Some pages are in colour.
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Citation
Nasser, Y. (2007). Enteric glial cells play a role in neuronal signalling and in inflammation in the gastrointestinal tract (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/1745