Alpha2-Adrenergic Receptors in Intestinal Epithelial Cells: Mechanisms of Signaling, Role, and Regulation

Abstract

Studies on different animal species have demonstrated the predominant importance of α2-adrenergic receptors (a2-ARs) in mediating the effects of catecholamines on intestinal functions. Several clinical trials have also pointed out the interest of proabsorptive and antisecretory properties of clonidine for the treatment of diabetic or cancer therapy-related diarrhea. Binding experiments and RNase protection assays showed that epithelial cells of human intestinal mucosa express a2A-AR subtype and that this receptor is abundant in immature and proliferative cells from the crypts. Although a2-agonists cause inhibition of cAMP production, the mechanisms whereby transepithelial transport of water and electrolytes is affected are not completely understood. The aim of this presentation is to review studies carried out on human cancerous intestinal cell-lines naturally expressing the a2A-AR or permanently transfected with the a2C10 gene. Beside confirming the inverse relationship between enterocytic differentiation and receptor expression, data obtained on these in vitro models provide insights into the signaling pathways and regulation of a2A-ARs in epithelial cells. They also support a role for this receptor in the control of proliferative and absorptive activity of intestinal epithelium.