Investigation into the role of the second and third extracellular loop domains of the glucagon-like peptide-1 receptor in ligand binding and activation

2002 ◽  
Vol 30 (3) ◽  
pp. A96-A96
Author(s):  
S. Y. Al-Sabah ◽  
D. Donnelly
Keyword(s):  
Ligand Binding ◽  
Extracellular Loop ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Loop Domains

Analysis of role of aromatic residues in extracellular loop 2 of Prokineticin receptor 2 in ligand binding probed with genetically encoded photo-crosslinkers

2021 ◽  
pp. 183549
Author(s):  
Maria Rosaria Fullone ◽  
Roberta Lattanzi ◽  
Daniela Maftei ◽  
Maria Carmela Bonaccorsi ◽  
Rossella Miele
Keyword(s):  
Ligand Binding ◽  
Extracellular Loop ◽  
Aromatic Residues ◽  
Loop 2

scholarly journals Residues within the Transmembrane Domain of the Glucagon-Like Peptide-1 Receptor Involved in Ligand Binding and Receptor Activation: Modelling the Ligand-Bound Receptor

2011 ◽  
Vol 25 (10) ◽  
pp. 1804-1818 ◽  
Author(s):  
K. Coopman ◽  
R. Wallis ◽  
G. Robb ◽  
A. J. H. Brown ◽  
G. F. Wilkinson ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Structural Model ◽  
Transmembrane Domain ◽  
Transmembrane Helix ◽  
Receptor Activation ◽  
Agonist Affinity ◽  
Camp Generation ◽  
N Terminus ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The C-terminal regions of glucagon-like peptide-1 (GLP-1) bind to the N terminus of the GLP-1 receptor (GLP-1R), facilitating interaction of the ligand N terminus with the receptor transmembrane domain. In contrast, the agonist exendin-4 relies less on the transmembrane domain, and truncated antagonist analogs (e.g. exendin 9–39) may interact solely with the receptor N terminus. Here we used mutagenesis to explore the role of residues highly conserved in the predicted transmembrane helices of mammalian GLP-1Rs and conserved in family B G protein coupled receptors in ligand binding and GLP-1R activation. By iteration using information from the mutagenesis, along with the available crystal structure of the receptor N terminus and a model of the active opsin transmembrane domain, we developed a structural receptor model with GLP-1 bound and used this to better understand consequences of mutations. Mutation at Y152 [transmembrane helix (TM) 1], R190 (TM2), Y235 (TM3), H363 (TM6), and E364 (TM6) produced similar reductions in affinity for GLP-1 and exendin 9–39. In contrast, other mutations either preferentially [K197 (TM2), Q234 (TM3), and W284 (extracellular loop 2)] or solely [D198 (TM2) and R310 (TM5)] reduced GLP-1 affinity. Reduced agonist affinity was always associated with reduced potency. However, reductions in potency exceeded reductions in agonist affinity for K197A, W284A, and R310A, while H363A was uncoupled from cAMP generation, highlighting critical roles of these residues in translating binding to activation. Data show important roles in ligand binding and receptor activation of conserved residues within the transmembrane domain of the GLP-1R. The receptor structural model provides insight into the roles of these residues.

scholarly journals Ileal short-chain fatty acids inhibit gastric motility by a humoral pathway

2000 ◽  
Vol 279 (5) ◽  
pp. G925-G930 ◽  
Author(s):  
G. Cuche ◽  
J. C. Cuber ◽  
C. H. Malbert
Keyword(s):  
Gastric Motility ◽  
Short Chain Fatty Acid ◽  
Peptide Yy ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Maximal Amplitude ◽  
Inhibiting Factor ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The aim of this study was to evaluate the nervous and humoral pathways involved in short-chain fatty acid (SCFA)-induced ileal brake in conscious pigs. The role of extrinsic ileal innervation was evaluated after SCFA infusion in innervated and denervated Babkin's ileal loops, and gastric motility was measured with strain gauges. Peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) concentrations were evaluated in both situations. The possible involvement of absorbed SCFA was tested by using intravenous infusion of acetate. Ileal SCFA infusion in the intact terminal ileum decreased the amplitude of distal and terminal antral contractions (33 ± 1.2 vs. 49 ± 1.2% of the maximal amplitude recorded before infusion) and increased their frequency (1.5 ± 0.11 vs. 1.3 ± 0.10/min). Similar effects were observed during SCFA infusion in ileal innervated and denervated loops (amplitude, 35 ± 1.0 and 34 ± 0.8 vs. 47 ± 1.3 and 43 ± 1.2%; frequency, 1.4 ± 0.07 and 1.6 ± 0.06 vs. 1.1 ± 0.14 and 1.0 ± 0.12/min). Intravenous acetate did not modify the amplitude and frequency of antral contractions. PYY but not GLP-1 concentrations were increased during SCFA infusion in innervated and denervated loops. In conclusion, ileal SCFA inhibit distal gastric motility by a humoral pathway involving the release of an inhibiting factor, which is likely PYY.

scholarly journals The Role of Self-Monitoring of Blood Glucose in Glucagon-like Peptide-1-Based Treatment Approaches: A European Expert Recommendation

2012 ◽  
Vol 6 (3) ◽  
pp. 665-673 ◽  
Author(s):  
Oliver Schnell ◽  
Hasan Alawi ◽  
Tadej Battelino ◽  
Antonio Ceriello ◽  
Peter Diem ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Self Monitoring ◽  
Treatment Approaches ◽  
Expert Recommendation ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Second Extracellular Loop of Human Glucagon-like Peptide-1 Receptor (GLP-1R) Has a Critical Role in GLP-1 Peptide Binding and Receptor Activation

2011 ◽  
Vol 287 (6) ◽  
pp. 3642-3658 ◽  
Author(s):  
Cassandra Koole ◽  
Denise Wootten ◽  
John Simms ◽  
Laurence J. Miller ◽  
Arthur Christopoulos ◽  
...  
Keyword(s):  
Critical Role ◽  
Peptide Binding ◽  
Receptor Activation ◽  
Extracellular Loop ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1
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