Motilin receptors in the human antrum

Motilin is an intestinal peptide that stimulates contraction of gut smooth muscle. The motilin receptor has not been cloned yet, but motilin-receptor agonists appear to be potent prokinetic agents for the treatment of dysmoti lity disorders. The aim of this study was to determine neural or muscular l ocalization of motilin receptors in human upper gastrointestinal tract and to investigate their pharmacological characteristics. The binding of I-125- labeled motilin to tissue membranes prepared from human stomach and duoden um was studied; rabbit tissues were used for comparison. Solutions enriched in neural synaptosomes or in smooth muscle plasma membranes were obtained. Various motilin analogs were used to displace the motilin radioligand from the various tissue membranes. The highest concentration of human motilin r eceptors was found in the antrum, predominantly in the neural preparation. Human motilin receptors were sensitive to the NH2-terminal portion of the m otilin molecule, but comparison with rabbit showed that both species had sp ecific affinities for various motilin analogs [i.e., Mot-(1-9), Mot-(1-12), Mot-(1-12) (CH2NH)(10-11), and erythromycin]. Motilin receptors obtained f rom synaptosomes or muscular plasma membranes of human antrum expressed dif ferent affinity for two motilin-receptor agonists, Mot-(1-12) and Mot-(1-12 ) (CH2NH)(10-11), suggesting that they correspond to specific receptor subt ypes. We conclude that human motilin receptors are located predominantly in nerves of the antral wall, are functionally (and probably structurally) di fferent from those found in other species such as the rabbit, and express s pecific functional (and probably structural) characteristics dependent on t heir localization on antral nerves or muscles, suggesting the existence of specific receptor subtypes, potentially of significant physiological or pha rmacological relevance.