The neuropeptide substance P (SP) is mediated by the NK1-R desensitize and resensitize, which may be associated with NK1-R endocytosis and recycling. SP and the NK1-R have internalized into the same clathrin immunoreactive vesicles and then sorted into different compartments. SP is intact at the cell surface and in early endosomes but slowly degraded in perinuclear vesicles. SP induces clathrin-dependent internalization of the NK1-R. The SP/NK1-R complex dissociates in acidified endosomes. SP induces the internalization of the NK1-R both in transfected epithelial cells [1].