Abstract
The ability of enterocytes to secrete electrolytes and water into the intestinal lumen represents a critical feature of mucosal defense. During disease, this function may be altered and may initiate or exacerbate pathological conditions. Although many of the intracellular mechanisms linking stimulation to secretion have been elucidated, novel pathways continue to be revealed. These pathways provide potential for therapeutic manipulation of cellular function. In addition, the importance of the microenvironment surrounding enterocytes is increasingly being acknowledged, and the interactions between epithelial cells and their milieu are proving to be essential to the regulation of secretory function, both in health and disease. In this way, epithelial ion transport functions can be modulated by mediators released from neighboring nerves, inflammatory cells, and pathogens, or by endocrine factors. Much interest has recently been elicited by the discovery that proteinases can regulate cellular functions through the activation of proteinaseโactivated receptors (PARs). Because of the abundance of proteases within the gastrointestinal tract, particularly in the setting of development, inflammation, and healing, it is likely that PARs have an important role to play in these processes. PARs have been localized to a variety of cell types in the gastrointestinal tract, and have been shown to influence epithelial secretory function on several levels. In this review, we discuss the mechanisms by which proteases and PARs regulate intestinal secretory function, and the manner in which these modulations might contribute to inflammatory processes. Drug Dev. Res. 59:386โ394, 2003. ยฉ 2003 WileyโLiss, Inc.