Receptors in interstitial cells of Cajal: identification and possible physiological roles

Interstitial cells of Cajal (ICCs) are specialized cells of the gastrointestinal tract forming distinct populations depending on their location in the gut wall. Morphological observations and functional data have led to the hypothesis of two functions for the ICCs: (1) as pacemakers of the rhythmic activity; (2) as intermediaries in neural inputs to the muscle. The identification of specific receptors on the ICCs has represented an important step in the knowledge of these cells. Immunohistochemical labeling of these receptors provided information on both ICC morphology and contacts (particularly those with nerve endings) and on the functions of these cells. All ICC possess the Kit receptor, which represents the best tool to identify these cells under the light microscope. It has been demonstrated that this receptor is essential for ICC differentiation, and, by using mutant mice lacking the Kit-related gene, it has been possible to discriminate among all the ICC those with a primary role as pacemakers. The ileal ICC, in particular those at the deep muscular plexus, express the tachykinin receptor NK1 and a subtype of somatostatin receptors and contain nitric oxide synthase. All these data support a primary role of these ICC in neural transmission.