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Science 25 June 1999:
Vol. 284. no. 5423, pp. 2184 - 2188
DOI: 10.1126/science.284.5423.2184
Prev | Table of Contents

Reports

Receptor for Motilin Identified in the Human Gastrointestinal System

Scott D. Feighner, 1* Carina P. Tan, 1* Karen Kulju McKee, 1* Oksana C. Palyha, 1 Donna L. Hreniuk, 1 Sheng-Shung Pong, 1 Christopher P. Austin, 3 David Figueroa, 3 Douglas MacNeil, 1 Margaret A. Cascieri, 1 Ravi Nargund, 2 Raman Bakshi, 2 Mark Abramovitz, Rino Stocco, Stacia Kargman, Gary O'Neill, Lex H. T. Van Der Ploeg, 1 Jilly Evans, Arthur A. Patchett, 2 Roy G. Smith, 5 Andrew D. Howard 1dagger

Motilin is a 22-amino acid peptide hormone expressed throughout the gastrointestinal (GI) tract of humans and other species. It affects gastric motility by stimulating interdigestive antrum and duodenal contractions. A heterotrimeric guanosine triphosphate-binding protein (G protein)-coupled receptor for motilin was isolated from human stomach, and its amino acid sequence was found to be 52 percent identical to the human receptor for growth hormone secretagogues. The macrolide antibiotic erythromycin also interacted with the cloned motilin receptor, providing a molecular basis for its effects on the human GI tract. The motilin receptor is expressed in enteric neurons of the human duodenum and colon. Development of motilin receptor agonists and antagonists may be useful in the treatment of multiple disorders of GI motility.

1 Department of Metabolic Disorders,
2 Department of Medicinal Chemistry, Merck Research Laboratories, Building RY-80Y-265, 126 East Lincoln Avenue, Rahway, NJ 07065, USA.
3 Department of Human Genetics, Merck Research Laboratories, Sumneytown Pike, West Point, PA 19486, USA. 4Department of Biochemistry and Molecular Biology, Merck-Frosst Center for Therapeutic Research, 16711 TransCanada Highway, Kirkland, Quebec H9H 3L1, Canada.
5 Huffington Center on Aging and Department of Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030-3498, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: howarda{at}merck.com

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