The precise functions of CART peptides released by enteric CART-expressing neurons in the ENS are yet to be determined (Ekblad, 2006). There has been a lack of direct evidence regarding a role of locally produced CART in classical neurotransmission within the GI tract, where intestinal motility as measured by contractile or relaxatory responses was unaffected by CART peptide application when motor activity studies were performed in vitro on muscle strips from stomach, small and large intestine (Ekblad et al., 2003). Notably, exceptions to the above may include specific CART-evoked colonic responses, such as the attenuation of nitric oxide-induced intestinal relaxation (Ekblad et al., 2003; Ekblad, 2006), as well as the apparent stimulation of colonic transit, an indirect measure of colonic motor function (Tebbe et al., 2004). In spite of the confined documentation of CART involvement in brain-gut interaction and the indeterminate functional role of enteric CART, accumulating evidence propose a role of CART in intestinal adaptation, where the survival and maintenance of enteric neurons is promoted (Ekblad et al., 2003; Ekblad, 2006). Such neuroprotective property (Ekblad, 2006; Zhang et al., 2012) and intestinal plasticity has been inferred from upregulated CART expression and increased CART-expressing neurons in atrophic intestine and cultured myenteric neurons respectively, conditions indicative of neuronal stress or injury (Ekblad et al., 2003; Ekblad, 2006). In sum, gastric involvement of CART has been evident through discrete histological and physiological experiments, whilst further detailed characterization of distribution and functions may contribute to a comprehensive understanding of the specific roles of enteric CART.