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Identification of genes for the ghrelin and motilin receptors and a novel related gene in fish, and stimulation of intestinal motility in zebrafish (Danio rerio) by ghrelin and motilin.

Journal article
Authors Catharina Olsson
Joanna D Holbrook
Giulia Bompadre
Elisabeth Jönsson
Charles H V Hoyle
Gareth J Sanger
Susanne Holmgren
Paul L R Andrews
Published in General and comparative endocrinology
Volume 155
Issue 1
Pages 217-26
ISSN 0016-6480
Publication year 2008
Published at Department of Zoology
Pages 217-26
Language en
Keywords Amino Acid Sequence, Animals, Cloning, Molecular, Electric Stimulation, Erythromycin, pharmacology, Female, Fishes, genetics, Gastrointestinal Motility, drug effects, Ghrelin, pharmacology, physiology, Humans, Male, Molecular Sequence Data, Motilin, pharmacology, physiology, Phylogeny, Receptors, Gastrointestinal Hormone, genetics, Receptors, Ghrelin, genetics, Receptors, Neuropeptide, genetics, Sequence Homology, Zebrafish, genetics, physiology
Subject categories Animal physiology


In mammals ghrelin has a diverse range of effects including stimulation of gut motility but although present in teleost fish its effects on motility have not been investigated. The present study used bioinformatics to search for fish paralogues of the ghrelin receptor and the closely related motilin receptor, and investigated the effects of ghrelin and motilin on gut motility in zebrafish, Danio rerio. Fish paralogues of the human ghrelin and motilin receptor genes were identified, including those from the zebrafish. In addition, a third gene was identified in three species of pufferfish (the only fish genome completely sequenced), which is distinct from the ghrelin and motilin receptors but more closely aligned to these receptors relative to other G-protein coupled receptors. Immunohistochemistry demonstrated strong ghrelin receptor-like reactivity in the muscle of the zebrafish intestine. In isolated intestinal bulb and mid/distal intestine preparations, ghrelin, motilin, and the motilin receptor agonist erythromycin all evoked contraction; these responses ranged between 9% and 51% of the contractions evoked by carbachol (10(-6) M). There were some variations in the concentrations found to be active in the different tissues, e.g., whereas motilin and rat ghrelin caused contraction of the intestinal bulb circular muscle at concentrations as low as 10(-8) M, human ghrelin (10(-8) to 10(-6) M) was without activity. Neither ghrelin (10(-7) M) nor erythromycin (10(-5) M) affected the contractions evoked by electrical field stimulation. The results suggest that both ghrelin and motilin can regulate intestinal motility in zebrafish and most likely other teleosts, and are discussed in relation to the evolution of these regulatory peptides.

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