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Am J Physiol Gastrointest Liver Physiol 278: G18-G23, 2000;
0193-1857/00 $5.00
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Vol. 278, Issue 1, G18-G23, January 2000

Motilin receptors in the human antrum

Paul Miller1, André Roy2, Serge St-Pierre3, Michel Dagenais2, Réal Lapointe2, and Pierre Poitras1

1 Gastrointestinal Unit and 2 Department of Surgery, Centre Hospitalier de l'Université de Montréal; and 3 Department of Chemistry, Université du Québec à Montréal, Montreal, Quebec, Canada H2X 3J4

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 dysmotility disorders. The aim of this study was to determine neural or muscular localization of motilin receptors in human upper gastrointestinal tract and to investigate their pharmacological characteristics. The binding of 125I-labeled motilin to tissue membranes prepared from human stomach and duodenum 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 receptors was found in the antrum, predominantly in the neural preparation. Human motilin receptors were sensitive to the NH2-terminal portion of the motilin molecule, but comparison with rabbit showed that both species had specific affinities for various motilin analogs [i.e., Mot-(1---9), Mot-(1---12), Mot-(1---12) (CH2NH)10-11, and erythromycin]. Motilin receptors obtained from synaptosomes or muscular plasma membranes of human antrum expressed different affinity for two motilin-receptor agonists, Mot-(1---12) and Mot-(1---12) (CH2NH)10-11, suggesting that they correspond to specific receptor subtypes. We conclude that human motilin receptors are located predominantly in nerves of the antral wall, are functionally (and probably structurally) different from those found in other species such as the rabbit, and express specific functional (and probably structural) characteristics dependent on their localization on antral nerves or muscles, suggesting the existence of specific receptor subtypes, potentially of significant physiological or pharmacological relevance.

gastrointestinal motility; regulatory peptides; receptor subtypes


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