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Adhesion GPCRs are widely expressed throughout the subsections of the gastrointestinal tract.

Badiali L, Cedernaes J, Olszewski PK, Nylander O, Vergoni AV, Schiöth HB - BMC Gastroenterol (2012)

Bottom Line: G protein-coupled receptors (GPCRs) represent one of the largest families of transmembrane receptors and the most common drug target.The distribution of these receptors has not been characterized in detail in the gastrointestinal (GI) tract.Most notably, almost all Group III members were ubiquitously expressed, while the restricted expression was characteristic for the majority of group VII members, hinting at more specific/localized roles for some of these receptors.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neuroscience, Uppsala University, BMC, Uppsala, SE 75124, Sweden.

ABSTRACT

Background: G protein-coupled receptors (GPCRs) represent one of the largest families of transmembrane receptors and the most common drug target. The Adhesion subfamily is the second largest one of GPCRs and its several members are known to mediate neural development and immune system functioning through cell-cell and cell-matrix interactions. The distribution of these receptors has not been characterized in detail in the gastrointestinal (GI) tract. Here we present the first comprehensive anatomical profiling of mRNA expression of all 30 Adhesion GPCRs in the rat GI tract divided into twelve subsegments.

Methods: Using RT-qPCR, we studied the expression of Adhesion GPCRs in the esophagus, the corpus and antrum of the stomach, the proximal and distal parts of the duodenum, ileum, jejunum and colon, and the cecum.

Results: We found that twenty-one Adhesion GPCRs (70%) had a widespread (expressed in five or more segments) or ubiquitous (expressed in eleven or more segments) distribution, seven (23%) were restricted to a few segments of the GI tract and two were not expressed in any segment. Most notably, almost all Group III members were ubiquitously expressed, while the restricted expression was characteristic for the majority of group VII members, hinting at more specific/localized roles for some of these receptors.

Conclusions: Overall, the distribution of Adhesion GPCRs points to their important role in GI tract functioning and defines them as a potentially crucial target for pharmacological interventions.

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Related in: MedlinePlus

GPCRs with limited expression along the GI tract. Each panel refers to one GPCR showing three pieces of information: group of belonging, N terminal region and relative expression in twelve segments of the GI tract. Expression levels are relative for each gene (maximal level of expression set to 1). Values are plotted as the mean ± SD; n = 3. GPR111, GPR113, GPR115 were only expressed in one sub-segment: the expression value was arbitrarily set to 1 to indicate the presence of expression. Abbreviations for N-termini moieties: GPS, GPCR proteolytic site; HBD, hormone-binding domain; TSP1, thrombospondin; PTX, pentraxin domain. Glycosylation sites (NXS or NXT tripeptide sequences that conform to the consensus sequence for N-linked glycosylation) are shown as small circles attached to the N-termini stretches; E, esophagus; F, corpus of the stomach; A, antrum of the stomach; D1 and D2, proximal and distal parts of the duodenum; J1 and J2, proximal and distal parts of the jejunum; I1 and I2, proximal and distal parts of the ileum; C, cecum; K1 and K2, proximal and distal parts of the colon.
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Figure 4: GPCRs with limited expression along the GI tract. Each panel refers to one GPCR showing three pieces of information: group of belonging, N terminal region and relative expression in twelve segments of the GI tract. Expression levels are relative for each gene (maximal level of expression set to 1). Values are plotted as the mean ± SD; n = 3. GPR111, GPR113, GPR115 were only expressed in one sub-segment: the expression value was arbitrarily set to 1 to indicate the presence of expression. Abbreviations for N-termini moieties: GPS, GPCR proteolytic site; HBD, hormone-binding domain; TSP1, thrombospondin; PTX, pentraxin domain. Glycosylation sites (NXS or NXT tripeptide sequences that conform to the consensus sequence for N-linked glycosylation) are shown as small circles attached to the N-termini stretches; E, esophagus; F, corpus of the stomach; A, antrum of the stomach; D1 and D2, proximal and distal parts of the duodenum; J1 and J2, proximal and distal parts of the jejunum; I1 and I2, proximal and distal parts of the ileum; C, cecum; K1 and K2, proximal and distal parts of the colon.

Mentions: A total of twelve GPCRs (40%) were found to be ubiquitous along the GI system (expressed in at least eleven segments – Figure 2), nine GPCRs (30%) had widespread expression (detected in at least five segments – Figure 3), seven GPCRs (23%) had restricted expression (transcript found in no more than four segments – Figure 4) and two GPCRs were not detected in any segments. The ubiquitously expressed genes (Figure 2) consisted of two members from Group II, namely GPR56 and GPR97 (although neither was expressed in the esophagus), all but one (EMR4) of the members from Group III (LEC1, LEC2, LEC3, ETL, EMR1, CD97), two members from Group IV (GPR124 and GPR125; the third member GPR123 could not be detected in any segment), GPR133 from Group V, and GPR116 from Group VII.


Adhesion GPCRs are widely expressed throughout the subsections of the gastrointestinal tract.

Badiali L, Cedernaes J, Olszewski PK, Nylander O, Vergoni AV, Schiöth HB - BMC Gastroenterol (2012)

GPCRs with limited expression along the GI tract. Each panel refers to one GPCR showing three pieces of information: group of belonging, N terminal region and relative expression in twelve segments of the GI tract. Expression levels are relative for each gene (maximal level of expression set to 1). Values are plotted as the mean ± SD; n = 3. GPR111, GPR113, GPR115 were only expressed in one sub-segment: the expression value was arbitrarily set to 1 to indicate the presence of expression. Abbreviations for N-termini moieties: GPS, GPCR proteolytic site; HBD, hormone-binding domain; TSP1, thrombospondin; PTX, pentraxin domain. Glycosylation sites (NXS or NXT tripeptide sequences that conform to the consensus sequence for N-linked glycosylation) are shown as small circles attached to the N-termini stretches; E, esophagus; F, corpus of the stomach; A, antrum of the stomach; D1 and D2, proximal and distal parts of the duodenum; J1 and J2, proximal and distal parts of the jejunum; I1 and I2, proximal and distal parts of the ileum; C, cecum; K1 and K2, proximal and distal parts of the colon.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3526421&req=5

Figure 4: GPCRs with limited expression along the GI tract. Each panel refers to one GPCR showing three pieces of information: group of belonging, N terminal region and relative expression in twelve segments of the GI tract. Expression levels are relative for each gene (maximal level of expression set to 1). Values are plotted as the mean ± SD; n = 3. GPR111, GPR113, GPR115 were only expressed in one sub-segment: the expression value was arbitrarily set to 1 to indicate the presence of expression. Abbreviations for N-termini moieties: GPS, GPCR proteolytic site; HBD, hormone-binding domain; TSP1, thrombospondin; PTX, pentraxin domain. Glycosylation sites (NXS or NXT tripeptide sequences that conform to the consensus sequence for N-linked glycosylation) are shown as small circles attached to the N-termini stretches; E, esophagus; F, corpus of the stomach; A, antrum of the stomach; D1 and D2, proximal and distal parts of the duodenum; J1 and J2, proximal and distal parts of the jejunum; I1 and I2, proximal and distal parts of the ileum; C, cecum; K1 and K2, proximal and distal parts of the colon.
Mentions: A total of twelve GPCRs (40%) were found to be ubiquitous along the GI system (expressed in at least eleven segments – Figure 2), nine GPCRs (30%) had widespread expression (detected in at least five segments – Figure 3), seven GPCRs (23%) had restricted expression (transcript found in no more than four segments – Figure 4) and two GPCRs were not detected in any segments. The ubiquitously expressed genes (Figure 2) consisted of two members from Group II, namely GPR56 and GPR97 (although neither was expressed in the esophagus), all but one (EMR4) of the members from Group III (LEC1, LEC2, LEC3, ETL, EMR1, CD97), two members from Group IV (GPR124 and GPR125; the third member GPR123 could not be detected in any segment), GPR133 from Group V, and GPR116 from Group VII.

Bottom Line: G protein-coupled receptors (GPCRs) represent one of the largest families of transmembrane receptors and the most common drug target.The distribution of these receptors has not been characterized in detail in the gastrointestinal (GI) tract.Most notably, almost all Group III members were ubiquitously expressed, while the restricted expression was characteristic for the majority of group VII members, hinting at more specific/localized roles for some of these receptors.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neuroscience, Uppsala University, BMC, Uppsala, SE 75124, Sweden.

ABSTRACT

Background: G protein-coupled receptors (GPCRs) represent one of the largest families of transmembrane receptors and the most common drug target. The Adhesion subfamily is the second largest one of GPCRs and its several members are known to mediate neural development and immune system functioning through cell-cell and cell-matrix interactions. The distribution of these receptors has not been characterized in detail in the gastrointestinal (GI) tract. Here we present the first comprehensive anatomical profiling of mRNA expression of all 30 Adhesion GPCRs in the rat GI tract divided into twelve subsegments.

Methods: Using RT-qPCR, we studied the expression of Adhesion GPCRs in the esophagus, the corpus and antrum of the stomach, the proximal and distal parts of the duodenum, ileum, jejunum and colon, and the cecum.

Results: We found that twenty-one Adhesion GPCRs (70%) had a widespread (expressed in five or more segments) or ubiquitous (expressed in eleven or more segments) distribution, seven (23%) were restricted to a few segments of the GI tract and two were not expressed in any segment. Most notably, almost all Group III members were ubiquitously expressed, while the restricted expression was characteristic for the majority of group VII members, hinting at more specific/localized roles for some of these receptors.

Conclusions: Overall, the distribution of Adhesion GPCRs points to their important role in GI tract functioning and defines them as a potentially crucial target for pharmacological interventions.

Show MeSH
Related in: MedlinePlus