title: Demonstration and characterization of motilin-binding sites in the rabbit cerebellum.
abstract: This is the first report on central motilin receptors. Autoradiography on cerebellar slices revealed specific motilin-binding sites in the molecular layer of the cortex. Scatchard analysis of cold saturation studies showed the existence of a high-(pKd,hi = 9.07 +/- 0.09, where pKd is the negative logarithm of the dissociation constant) and a low-affinity binding site (pKd,lo = 6.56 +/- 0.09). Similar affinities were found with rabbit motilin and with the porcine (po) antagonist [Phe3, Leu13]po-motilin. Feline and canine motilin had a markedly lower affinity for the low-affinity site (pKd,lo = 5.29 and 4.58, respectively); chicken motilin had a lower affinity for both sites (pKd,hi = 8.36, pKd,lo = 3.97). Erythromycin A and its derivative N-trimethyl erythromycin A cnol ether also bound to cerebellar motilin receptors (pKd,hi = 7.29 and 8.91, respectively). Structure-activity studies with motilin fragments and the potency ranking of agonists suggest that a novel subtype receptor of motilin may exist in the brain. Guanosine 5'-O-(3-thiotriphosphate) (0.1 mM) reduced the number and the affinity for the high-affinity binding sites, which is evidence for G protein-coupled receptors. Our findings open new perspectives for the study of the physiological role of motilin.
authors.affiliation: Department of Pathophysiology, Katholieke Universiteit Leuven, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Depoortere
authors.forename: T L
authors.initials: TL
authors.lastname: Peeters
mesh_terms: D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001667:Binding, Competitive; D002415:Cats; D002531:Cerebellum / Q000378:metabolism*; D002645:Chickens; D004285:Dogs; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000378:metabolism; D009037:Motilin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism; D011817:Rabbits; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D010446:Peptide Fragments; D009037:Motilin; C008680:motilin, Nle(13)-; D019204:GTP-Binding Proteins