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Journal of Histochemistry and Cytochemistry
Volume 52 (1): 53-64, 2004
Copyright ©The Histochemical Society, Inc.

Individual Subtypes of Enteroendocrine Cells in the Mouse Small Intestine Exhibit Unique Patterns of Inositol 1,4,5-trisphosphate Receptor Expression

Songyan Wang, Jianfeng Liu, Lin Li and Burton M. Wice

Department of Internal Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, Saint Louis, Missouri

Correspondence to: Burton M. Wice, PhD, Dept. of Internal Medicine, Division of Endocrinology, Metabolism and Lipid Research, Washington U. School of Medicine, Campus Box 8127, 660 South Euclid Avenue, St Louis, MO 63110. E-mail: bwice{at}im.wustl.edu

Enteroendocrine cells are a complex population of intestinal epithelial cells whose hormones play critical roles in regulating gastrointestinal and whole-animal physiology. There are many subpopulations of enteroendocrine cells based on the major hormone(s) produced by individual cells. Intracellular calcium plays a critical role in regulating hormone release. Inositol 1,4,5-trisphophate (IP3) receptors regulate calcium mobilization from endoplasmic reticulum-derived calcium stores in many endocrine and excitatory cells and are expressed in the intestine. However, the specific subtypes of enteroendocrine cells that express these receptors have not been reported. Immunohistochemical (IHC) studies revealed that enteroendocrine cells did not express detectable levels of type 2 IP3 receptors, whereas nearly all enteroendocrine cells that produced chromogranin A and/or serotonin expressed type 1 and type 3 IP3 receptors. Conversely, enteroendocrine cells that produced glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, cholecystokinin, or somatostatin did not express detectable levels of any IP3 receptors. Subsets of enteroendocrine cells that produced substance P or secretin expressed type 1 (33% or 18%, respectively) and type 3 (10% or 62%, respectively) IP3 receptors. Thus, different subtypes of enteroendocrine cells, as well as individual cells that express a particular hormone, exhibit remarkable heterogeneity in the molecular machineries that regulate hormone release in vivo. These results suggest that therapeutic agents can be developed that could potentially inhibit or promote secretion of hormones from specific subtypes of enteroendocrine cells. (J Histochem Cytochem 52:53–63, 2004)

Key Words: enteroendocrine cells • K-cells • GIP • hormone secretion • inositol 1,4,5-trisphosphate • receptor • IP3R


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