American Journal of Physiology. Gastrointestinal and Liver Physiology vol:272 issue:5 pages:G994-G999
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 pK(d) is the negative logarithm of the dissociation constant) and a low-affnity binding site (pK(d,lo) = 6.56 +/- 0.09). Similar affinities were found with rabbit motilin and with the porcine (po) antagonist [Phe(3),Leu(13)]po-motilin. Feline and canine motilin had a markedly lower affinity for the low-affinity site (pK(d,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 enol ether also bound to cerebellar motilin receptors (pK(d,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.