Molecular identification and characterization of the dog motilin receptor.
Motilin, a 22-amino acid peptide hormone secreted by endocrine cells of the intestinal mucosa, plays an important role in the regulation of gastrointestinal motility. The actions of motilin agonists have been extensively investigated in dogs due to physiological similarities between the dog and human alimentary tracts. The amino acid sequence of the dog motilin receptor, however, was previously unknown. We have cloned a cDNA from dog stomach corresponding to the motilin receptor. The deduced protein shared 71% and 72% sequence identity with the human and rabbit motilin receptors, respectively. Expression of the dog motilin receptor in CHO cells promoted the typical cellular responses to the agonists, motilin and erythromycin. The rank order of potency determined for these agonists was similar to that found for the human motilin receptor, with motilin being more potent than erythromycin. Immunohistochemistry of the dog stomach revealed that the motilin receptor was localized in neuronal cell bodies and fibers. This is the first study detailing the cloning, expression, and functional characterization of the dog motilin receptor. Determination of the full sequence and functional properties of the dog motilin receptor will provide useful information enabling us to interpret previous and future studies of motilin agonists in dogs.
Ohshiro
Hiroyuki
H
Pfizer Global Research and Development, Discovery Biology Research, 5-2 Taketoyo, Aichi, 470-2393, Japan. Hiroyuki.Oshiro@pfizer.com
Nonaka
Miki
M
Ichikawa
Katsuomi
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004285:Dogs; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D011964:Receptors, Gastrointestinal Hormone / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D013270:Stomach / Q000737:chemistry*
D018076:DNA, Complementary; D012333:RNA, Messenger; D011964:Receptors, Gastrointestinal Hormone; D018013:Receptors, Neuropeptide; C050802:motilin receptor