Spatial intensity distribution analysis quantifies the extent and regulation of homodimerization of the secretin receptor

Previous studies have indicated that the G protein-coupled secretin receptor is present as a homo-dimer, organized through symmetrical contacts in transmembrane domain IV, and that receptor dimerization is critical for high potency signalling by secretin. However, whether all of the receptor exists in the dimeric form or if this is regulated, is unclear. We used measures of quantal brightness of the secretin receptor tagged with monomeric enhanced green fluorescent protein (mEGFP) and Spatial Intensity Distribution Analysis to assess this. Calibration using cells expressing plasma membrane-anchored forms of mEGFP initially allowed demonstration that the Epidermal Growth Factor receptor is predominantly monomeric in the absence of ligand and whilst wild type receptor was rapidly converted to a dimeric form by ligand, a mutated form of this receptor remained monomeric. Equivalent studies showed that at moderate expression levels the secretin receptor exists as a mixture of monomeric and dimeric forms, with little evidence of higher-order complexity. However, sodium butyrate induced up-regulation of the receptor resulted in a shift from monomeric towards oligomeric organization. By contrast, a form of the secretin receptor containing a pair of mutations on the lipid-facing side of transmembrane domain IV was almost entirely monomeric. Down-regulation of the secretin receptor-interacting G protein Gαs did not alter receptor organization, indicating that dimerization is defined specifically by direct protein-protein interactions between copies of the receptor polypeptide, whilst short term treatment with secretin had no effect on organization of the wild type receptor but increased the dimeric proportion of the mutated receptor variant

Experimental Line Parameters of the b^(1)Σ^(+)_g ← X^(3)Σ^(-)_g Band of Oxygen Isotopologues at 760 nm Using Frequency-Stabilized Cavity Ring-Down Spectroscopy

Positions, intensities, self-broadened widths, and collisional narrowing coefficients of the oxygen isotopologues ^(16)O^(18)O, ^(16)O^(17)O, ^(17)O^(18)O, and ^(18)O^(18)O have been measured for the b^(1)Σg + ← X^(3)Σg − (0,0) band using frequency-stabilized cavity ring-down spectroscopy. Line positions of 156 P-branch transitions were referenced against the hyperfine components of the ^(39)K D_1 (4s ^(2)S_(1/2) → 4p ^(2)P_(1/2)) and D_2 (4s ^(2)S_(1/2) → 4p ^(2)P_(3/2)) transitions, yielding precisions of ~0.00005 cm^(−1) and absolute accuracies of 0.00030 cm^(−1) or better. New excited b^(1)Σg + state molecular constants are reported for all four isotopologues. The measured line intensities of the ^(16)O^(18)O isotopologue are within 2% of the values currently assumed in molecular databases. However, the line intensities of the ^(16)O^(17)O isotopologue show a systematic, J-dependent offset between our results and the databases. Self-broadening half-widths for the various isotopologues are internally consistent to within 2%. This is the first comprehensive study of the line intensities and shapes for the ^(17)O^(18)O or ^(18)O_2 isotopologues of the b^(1)Σg + ← X^(3)Σg − (0,0) band of O_2. The ^(16)O_2, ^(16)O^(18)O, and ^(16)O^(17)O line parameters for the oxygen A-band have been extensively revised in the HITRAN 2008 database using results from the present study

Cholecystokinin receptors in GtoPdb v.2023.1

Cholecystokinin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on CCK receptors [90]) are activated by the endogenous peptides cholecystokinin-8 (CCK-8), CCK-33, CCK-58 and gastrin (gastrin-17). There are only two distinct subtypes of CCK receptors, CCK1 and CCK2 receptors [64, 124], with some alternatively spliced forms most often identified in neoplastic cells. The CCK receptor subtypes are distinguished by their peptide selectivity, with the CCK1 receptor requiring the carboxyl-terminal heptapeptide-amide that includes a sulfated tyrosine for high affinity and potency, while the CCK2 receptor requires only the carboxyl-terminal tetrapeptide shared by each CCK and gastrin peptides. These receptors have characteristic and distinct distributions, with both present in both the central nervous system and peripheral tissues

Cholecystokinin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Cholecystokinin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on CCK receptors [89]) are activated by the endogenous peptides cholecystokinin-8 (CCK-8), CCK-33, CCK-58 and gastrin (gastrin-17). There are only two distinct subtypes of CCK receptors, CCK1 and CCK2 receptors [63, 123], with some alternatively spliced forms most often identified in neoplastic cells. The CCK receptor subtypes are distinguished by their peptide selectivity, with the CCK1 receptor requiring the carboxyl-terminal heptapeptide-amide that includes a sulfated tyrosine for high affinity and potency, while the CCK2 receptor requires only the carboxyl-terminal tetrapeptide shared by each CCK and gastrin peptides. These receptors have characteristic and distinct distributions, with both present in both the central nervous system and peripheral tissues

Preface

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Chronic unpredictable stress enhances cocaine-conditioned place preference in type 1 cannabinoid receptor knockout mice

Cannabinoid signaling via the CB1 receptor modulates the effects of drugs of abuse and the response to exposure to stressors. In addition, exposure to stressors can alter the effects of drugs of abuse. The present study examined the effects of exposure to chronic unpredictable stress (CUS) in CB1 receptor knockout mice (CB1 KO) and their wild-type (WT) littermates, using cocaine conditioned place preference (CPP) to compare their response to cocaine. Mice were untreated or exposed to two weeks of CUS. Following this period, the acquisition of a cocaine CPP was examined with one of three doses (3.2, 10.0 or 17.0 mg/kg) of cocaine. Untreated CB1 KO and WT mice both acquired the cocaine CPP; however, exposure to CUS enhanced the acquisition of the cocaine CPP in CB1 KO mice, but did not significantly alter the effects of cocaine in WT mice. Taken together, these findings support previous evidence suggesting a role for the CB1 receptor in the response to stress as well as in the effects of cocaine

Glucagon receptor family in GtoPdb v.2023.1

The glucagon family of receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on the Glucagon receptor family [165]) are activated by the endogenous peptide (27-44 aa) hormones glucagon, glucagon-like peptide 1, glucagon-like peptide 2, glucose-dependent insulinotropic polypeptide (also known as gastric inhibitory polypeptide), GHRH and secretin. One common precursor (GCG) generates glucagon, glucagon-like peptide 1 and glucagon-like peptide 2 peptides [121]. For a recent review on the current understanding of the structures of GLP-1 and GLP-1R, the molecular basis of their interaction, and the associated signaling events see de Graaf et al., 2016 [90]

Glucagon receptor family (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The glucagon family of receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on the Glucagon receptor family [159]) are activated by the endogenous peptide (27-44 aa) hormones glucagon, glucagon-like peptide 1, glucagon-like peptide 2, glucose-dependent insulinotropic polypeptide (also known as gastric inhibitory polypeptide), GHRH and secretin. One common precursor (GCG) generates glucagon, glucagon-like peptide 1 and glucagon-like peptide 2 peptides [116]. For a recent review on review the current understanding of the structures of GLP-1 and GLP-1R, the molecular basis of their interaction, and the signaling events associated with it, see de Graaf et al., 2016 [87]

Glucagon receptor family in GtoPdb v.2021.3

The glucagon family of receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on the Glucagon receptor family [162]) are activated by the endogenous peptide (27-44 aa) hormones glucagon, glucagon-like peptide 1, glucagon-like peptide 2, glucose-dependent insulinotropic polypeptide (also known as gastric inhibitory polypeptide), GHRH and secretin. One common precursor (GCG) generates glucagon, glucagon-like peptide 1 and glucagon-like peptide 2 peptides [119]. For a recent review on the current understanding of the structures of GLP-1 and GLP-1R, the molecular basis of their interaction, and the associated signaling events see de Graaf et al., 2016 [89]