The rabbit motilin receptor: molecular characterisation and pharmacology

Dass, Narinder B.; Hill, Jamal; Muir, Alison I.; Testa, T; Wise, Alan; Sanger, Gareth J.

doi:10.1038/sj.bjp.0705505

Cited by 68 publications

(79 citation statements)

References 22 publications

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“…Preliminary studies have shown that motilin can stimulate the ghrelin receptor, albeit at a low level. In contrast, ghrelin does not activate motilin receptor (53).…”

Section: A the Ghrelin Receptor Familymentioning

confidence: 93%

Ghrelin: Structure and Function

Kojima

Kangawa²

2005

Physiological Reviews

1,621

1,176

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Small synthetic molecules called growth hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. They act through the GHS-R, a G protein-coupled receptor whose ligand has only been discovered recently. Using a reverse pharmacology paradigm with a stable cell line expressing GHS-R, we purified an endogenous ligand for GHS-R from rat stomach and named it “ghrelin,” after a word root (“ghre”) in Proto-Indo-European languages meaning “grow.” Ghrelin is a peptide hormone in which the third amino acid, usually a serine but in some species a threonine, is modified by a fatty acid; this modification is essential for ghrelin's activity. The discovery of ghrelin indicates that the release of GH from the pituitary might be regulated not only by hypothalamic GH-releasing hormone, but also by ghrelin derived from the stomach. In addition, ghrelin stimulates appetite by acting on the hypothalamic arcuate nucleus, a region known to control food intake. Ghrelin is orexigenic; it is secreted from the stomach and circulates in the bloodstream under fasting conditions, indicating that it transmits a hunger signal from the periphery to the central nervous system. Taking into account all these activities, ghrelin plays important roles for maintaining GH release and energy homeostasis in vertebrates.

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“…Preliminary studies have shown that motilin can stimulate the ghrelin receptor, albeit at a low level. In contrast, ghrelin does not activate motilin receptor (53).…”

Section: A the Ghrelin Receptor Familymentioning

confidence: 93%

Ghrelin: Structure and Function

Kojima

Kangawa²

2005

Physiological Reviews

1,621

1,176

View full text Add to dashboard Cite

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“…This initial report revealed these novel GPCRs to be related to the ghrelin and neurotensin receptors. GPR38 has since been identified as the cognate receptor for motilin, a 22 amino acid peptide that regulates gastrointestinal (GI) motility [2,3]. In 2005, Zhang et al implicated GPR39 to be the receptor for obestatin [4], a peptide encoded by the ghrelin gene.…”

Section: Introductionmentioning

confidence: 99%

GPR39: a Zn2+-activated G protein-coupled receptor that regulates pancreatic, gastrointestinal and neuronal functions

Popovics

Stewart

2010

Cell. Mol. Life Sci.

102

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GPR39 is a vertebrate G protein-coupled receptor related to the ghrelin/neurotensin receptor subfamily. The receptor is expressed in a range of tissues including the pancreas, gut/gastrointestinal tract, liver, kidney and in some regions of the brain. GPR39 was initially thought to be the cognitive receptor for the peptide hormone, obestatin. However, subsequent in vitro studies have failed to demonstrate binding of this peptide to the receptor. Zn(2+) has been shown to be a potent stimulator of GPR39 activity via the Gα(q), Gα(12/13) and Gα(s) pathways. The potency and specificity of Zn(2+) in activating GPR39 suggest it to be a physiologically important agonist. GPR39 is now emerging as an important transducer of autocrine and paracrine Zn(2+) signals, impacting upon cellular processes such as insulin secretion, gastric emptying, neurotransmission and epithelial repair. This review focuses on the molecular, structural and biological properties of GPR39 and its various physiological functions.

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“…Concentrated peptide solutions (1 mg/ml) were prepared in PBS and stored as 20-l aliquots in Eppendorf vials at Ϫ80°C until use. Motilin concentrations used had previously been shown to elicit a response in vitro (10,28).…”

mentioning

confidence: 99%

Motilin stimulates preadipocyte proliferation and differentiation and adipocyte lipid storage

Miegueu

Cianflone

Richard

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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Miegueu P, Cianflone K, Richard D, St-Pierre DH. Motilin stimulates preadipocyte proliferation and differentiation and adipocyte lipid storage. Am J Physiol Endocrinol Metab 301: E758-E766, 2011. First published July 19, 2011 doi:10.1152/ajpendo.00089.2011Motilin is a circulating gastrointestinal peptide secreted primarily by duodenal mucosal M cells and recognized for its prokinetic effects on gastrointestinal tissues. Little information is available regarding effects on insulin/glucose homeostasis or adipocyte function. Our aim was to evaluate the effects of motilin on adipocyte proliferation, differentiation, lipolysis, and macronutrient uptake in adipocytes. 3T3-L1 cells and primary rat adipocytes were treated acutely and chronically with varying motilin concentrations, and effects were compared with vehicle alone (control), set as 100% for all assays. In preadipocytes, motilin stimulated proliferation ([ 3 H]thymidine incorporation) and mitochondrial activity (141 Ϯ 10%, P Ͻ 0.001 and 158 Ϯ 10%, respectively, P Ͻ 0.001), in a concentration-dependent manner. Chronic supplementation with motilin during differentiation further increased lipogenesis (Oil red O staining 191 Ϯ 27%, P Ͻ 0.05) and was associated with an upregulation of PPAR␥ (148 Ϯ 8%, P Ͻ 0.01), C/EBP␣ (142 Ϯ 17%, P Ͻ 0.05), and Cav3 (166 Ϯ 20%, P Ͻ 0.05) expression. In mature 3T3-L1 adipocytes motilin increased fatty acid uptake/incorporation (Յ202 Ϯ 12%; P Ͻ 0.01) and glucose uptake (146 Ϯ 9% P Ͻ 0.05) and decreased net fatty acid release (maximal Ϫ31%, P Ͻ 0.05) without influencing total lipolysis (glycerol release). Similar effects were obtained in primary rat adipocytes. Motilin acutely increased expression of PPAR␥, CEBP␤, DGAT1, and CD36 while decreasing adiponectin mRNA and secretion. In human adipose tissue, motilin receptor GPR38 correlated with HOMA-IR and GHSR1 (r ϭ 0.876, P Ͻ 0.0001). Motilin binding and fatty acid incorporation into adipocytes were inhibited by antagonists MB10 and [D-lys3]-GRP6 and PI 3-kinase inhibitor wortmannin. Taken together, these results suggest that motilin may directly influence adipocyte functions by stimulating energy storage. gastrointestinal hormones; peroxisome proliferator-activated receptor-␥; gene expression STRONG EVIDENCE SUGGESTS the neuroendocrine nature of many gastrointestinal (GI) peptides and their relevance in the regulation of important biological functions such as energy balance. The discovery of ghrelin in 1999 (18) provided evidence that a specific GI peptide could stimulate growth hormone secretion and appetite centrally besides influencing gut motility, glucose metabolism, adipogenesis, inflammation, and cardiovascular functions in the periphery (42). In contrast to ghrelin, there is limited information available regarding "long-discovered" GI peptides and their influence on the regulation of metabolic functions. Isolated and characterized in 1971, motilin is predominantly recognized for its prokinetic effects on gastric motility and emptying (5). Interestingly, motilin and ghrelin s...

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The rabbit motilin receptor: molecular characterisation and pharmacology

Cited by 68 publications

References 22 publications

Ghrelin: Structure and Function

Ghrelin: Structure and Function

GPR39: a Zn2+-activated G protein-coupled receptor that regulates pancreatic, gastrointestinal and neuronal functions

Motilin stimulates preadipocyte proliferation and differentiation and adipocyte lipid storage

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