Abstract
Orexins (orexin-A: ORX-A and orexin-B: ORX-B) are neuropeptides which regulate feeding and energy homeostasis. Our previous experiments with intracelluar recordings from myenteric plexus neurons and with intestinal contraction mesurements by Magnus method suggested that ORX-A contributed in the regulation of gut motility via enteric nervous system. Moreover, it was reported that ORX-A affected neuronal activity and synaptic transmission in the submucosal plexus. However, actions of ORXs on mucosal functions are not yet known. The present study investigated actions of ORXs on mucosal transport functions by measuring transmural short-circuit currents (Isc) using Ussing chamber technique in the guinea-pig small intestine. When ORX-A (10 nM to 100 nM) was applied to mucosal side of intesitinal submucosa-mucosa preparations made by removing muscularis and serosa, Isc was not changed. But when ORX-A was applied to submucosal side, Isc was transiently increased. This Isc change was inhibited by submucosal TTX. ORX-B (10 nM to 100 nM) induced smaller TTX-sensitive changes in Isc than ORX-A, when applied to submucosal side. These results suggest that ORXs stimulates mucosal transport by activating submucosal plexus neurons. Immunohistochemical localization of ORX receptors were also demonstrated using the same preparations. [Jpn J Physiol 54 Suppl:S200 (2004)]