A Cluster of Four Novel Human G Protein-Coupled Receptor Genes Occurring in Close Proximity to CD22 Gene on Chromosome 19q13.1

Sawzdargo, Marek; George, Susan R.; Nguyen, Tuan; Xu, Shijie; Kolakowski, Lee F.; O’Dowd, Brian F.

doi:10.1006/bbrc.1997.7513

Cited by 182 publications

(140 citation statements)

References 25 publications

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“…The rabbits were bled from the marginal ear vein, ten days after each immunization. After six immunizations, one of the three rabbits revealed a high titer antiserum (RY1494) against human GPR41 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), and was used for the present study.…”

Section: Methodsmentioning

confidence: 99%

Expression of short-chain fatty acid receptor GPR41 in the human colon

et al. 2009

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Short-chain fatty acids (SCFAs), including acetate, propionate and butyrate, are the most commonly found anions found in the monogastric mammalian large intestine, and are known to have a variety of physiological and pathophysiological effects on the gastrointestinal tract. We investigated the protein and mRNA expression levels of GPR41, a possible G protein coupled receptor for SCFA, using Western blot analysis and reverse transcriptase-polymerase chain reaction. We found that GPR41 protein and mRNA are expressed in human colonic mucosa. Immunohistochemistry for GPR41 showed that mucosal GPR41 protein is localized in cytoplasm of enterocytes and enteroendocrine cells. Moreover, GPR41-immunoreactive endocrine cells contained peptide YY but not serotonin or GPR43. The cellular population of GPR41 (0.01 ± 0.01 cells/crypt) was much smaller than that of GPR43 (0.33 ± 0.01 cells/crypt) in the human colon. However, the potency order of SCFA-induced phasic contraction of colonic smooth muscle that we previously reported is consistent with GPR41 (propionate ≧ butyrate > acetate) but not GPR43 (propionate = butyrate = acetate). Therefore, the present study suggests that GPR41 expressed in human colonic mucosa may function as a sensor for luminal SCFAs.Short-chain fatty acids (SCFA) are a major anion present in the large intestinal lumen of monogastric mammals including humans. SCFAs are produced during anaerobic bacterial fermentation of unabsorbed carbohydrates and dietary fibers. The concentration of SCFAs in human feces is reported to be approximately 100 mM, and are primarily comprised of acetate, propionate, and butyrate. Molar ratios of SCFAs in human fecal content are 50-60, 15-20, and 10-20 for acetate, propionate, and butyrate respectively (3, 22). Through absorption and metabolism of SCFAs, the host is able to salvage energy from food not digested in the upper intestine. Furthermore, luminal SCFAs have various physiological and pathophysiological effects in the gastrointestinal (GI) tract (4,10,17,19). In our previous studies, we demonstrated that SCFAs evoke two different effects on rat colonic smooth muscle in vitro (13)(14)(15). In the early phase, propionate and butyrate induced concentrationdependent phasic contractions in circular and longitudinal muscle, but acetate had no such effect (13-15). In the late phase, propionate induced a concentration-dependent increase in frequency of spontaneous contractions in circular (13) and longitudinal muscle (15), but butyrate did not affect the frequency of spontaneous longitudinal muscle contractions (15). On the other hand, acetate induced a

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Section: Methodsmentioning

confidence: 99%

Expression of short-chain fatty acid receptor GPR41 in the human colon

et al. 2009

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“…This search resulted in identification of a tandemly encoded intronless gene cluster on the CD22 gene localized on human chromosome locus 19q13.1 [7]. Subsequent sequencing of the gene and homology revealed the four novel GPCRs GPR40, GPR41, GPR42, and GPR43.…”

Section: Gpr41-gpr43mentioning

confidence: 99%

Fatty Acid Binding Receptors and Their Physiological Role in Type 2 Diabetes

Swaminath

2008

Archiv der Pharmazie

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G‐protein‐coupled receptors (GPCRs) respond to various physiological ligands such as photons, ions, and small molecules that include amines, fatty acids, and amino acids to peptides, proteins and steroids. Therefore, this family of proteins represents an attractive target for biopharmaceutical research [1]. The physiological role of fatty acids and other lipid molecules as important signal mediators is well studied in various metabolic pathways [2]. Acute administration of free fatty acids (FFAs) stimulates insulin release. Conversely, chronic exposure to high levels of free fatty acids leads to impairment of β cell function and lipotoxicity. However, the receptors through which these fatty acids and lipids act were unknown, until the identification of fatty acid binding receptors: GPR40, GPR41, GPR43, and GPR119. Based on their tissue‐expression profile, and pharmacologic analysis, the fatty acid binding receptors along with lipid binding receptor GPR119 are linked to diabetes and obesity. They play a critical role in the metabolic regulation of insulin release and glucose homeostasis. In this review, the mechanism of receptor activation, pharmacology, and the physiological functions of the fatty acid binding receptors will be discussed.

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“…The family of G-protein coupled free fatty acid receptors includes one group of molecules which share a moderate degree of structural homology and whose genes are all located within a closely aligned region of human chromosome 19 (19q13.1) [15]. These proteins display the typical seven-transmembrane domain organisation of G-protein coupled receptors and were originally termed GPR40, 41 & 43 before their endogenous ligands were known.…”

Section: Introductionmentioning

confidence: 99%

G-protein coupled receptors mediating long chain fatty acid signalling in the pancreatic beta-cell

Morgan¹,

Dhayal²

2009

Biochemical Pharmacology

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It is increasingly clear that some of the effects of both free and derivatised long chain fatty acids in pancreatic beta-cells are mediated by a group of G-protein coupled receptors. Some of these display close structural homology while others are more divergent. This Commentary reviews the expression and functional roles of three such molecules, GPR40, GPR119 and GPR120. GPR40 is the best characterised of this group and appears to mediate the acute stimulatory effects of long chain fatty acids on insulin secretion. GPR40 has also been proposed as a potential mediator of fatty acid toxicity but this is more controversial. GPR119 is also involved in stimulation of insulin secretion and responds primarily to ethanolamine derivatives of long chain fatty acids and also to some lysophospholipids rather than to free fatty acids. It may represent a useful target for the development of new insulin secretagogues aimed to enhance insulin release in patients with type 2 diabetes. GPR120 is the most enigmatic of the lipid responsive cell-surface receptors and its function remains to be established. It has been proposed to play a cytoprotective role in certain other cell types but it is unclear whether it fulfils a similar function in beta-cells.

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A Cluster of Four Novel Human G Protein-Coupled Receptor Genes Occurring in Close Proximity to CD22 Gene on Chromosome 19q13.1

Cited by 182 publications

References 25 publications

Expression of short-chain fatty acid receptor GPR41 in the human colon

Expression of short-chain fatty acid receptor GPR41 in the human colon

Fatty Acid Binding Receptors and Their Physiological Role in Type 2 Diabetes

G-protein coupled receptors mediating long chain fatty acid signalling in the pancreatic beta-cell

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