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In terms of structure, the motilin receptor has closest homology with the ghrelin receptor. Thus, the human motilin receptor shares 52% overall amino acid identity with the ghrelin receptor and 86% in the transmembrane regions [8,23-24]. However, differences between the N-terminus regions of these receptors means that their cognate peptide ligands do not readily activate each other [4,21]. In laboratory rodents, the gene encoding the motilin percursor appears to be absent, while the receptor appears to be a pseudogene [8,19]. Functions of motilin (MLN, P12872) are not usually detected in rodents, although brain and other responses to motilin and the macrolide alemcinal have been reported and the mechanism of these actions is obscure [15,17]. Notably, in some non-laboratory rodents (e.g. the North American kangaroo rat (Dipodomys) and mouse (Microdipodops) a functional form of motilin may exist but the motilin receptor is non-functional [11]. Marked differences in ligand affinities for the motilin receptor in dogs and humans may be explained by significant differences in receptor structure [20]. Note that for the complex macrolide structures, selectivity of action has often not been rigorously examined and other actions are possible (e.g. P2X inhibition by erythromycin; [26]). Small molecule motilin receptor agonists are now described [11,21,25]. The motilin receptor does not appear to have constitutive activity [9]. Although not proven, the existence of biased agonism at the receptor has been suggested [14,16,18]. A truncated 5-transmembrane structure has been identified but this is without activity when transfected into a host cell [6]. Receptor dimerisation has not been reported.