Alpha2A adrenoreceptor influence on intestinal epithelial stem cell proliferation

Abstract

The intestinal epithelium is critical for nutrient absorption, immune function, and hormone release. The mature cell types that are responsible for these functions are produced by crypt base columnar (CBC) stem cells located within the intestinal crypts. These stem cells constitutively divide to produce complete turnover of the entire intestinal epithelial layer every few days. The division of the CBC stem cells can be influenced by a variety of factors, including nutrient availability. There is research that suggests the sympathetic nervous system can contribute to changes in stem cell proliferation. However, it is not known whether this effect is direct via the CBC stem cells, or instead through an indirect mechanism. Thus, we tested whether CBC stem cells express alpha_2A adrenoreceptors (α_2A-ARs), a receptor subtype utilized by norepinephrine (NE; the primary neurotransmitter of the SNS) and whether NE induces proliferation of intestinal epithelial organoids in vitro. Results showed that α_2A-ARs mRNA is expressed in CBC stem cells and that there is a trend towards higher expression of α_2A-AR mRNA in CBC stem cells compared with other cells of the crypt. We also found a significant decrease in proliferation after application of NE to organoids in vitro (p<.05). These data support a role for the SNS in regulation of CBC stem cells proliferation, which may influence intestinal epithelial size and function as a whole.