Histamine H2 Receptor Biased Signaling Methods

Fernández, Natalia Cristina; Shayo, Carina; Davio, Carlos; Monczor, Federico

doi:10.1007/978-1-4939-6843-5_4

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“…A key advantage of such agonistic G protein-biased ligands is that they are unlikely to be internalized due to their low β-arrestin2 recruitment and therefore can also be applied to cells without taking any measures against internalization (e.g., hypotonic buffer). 36 The obtained pEC 50 values were in good agreement with the K i values from the radioligand competition-binding assays, especially in the case of the mini-G protein recruitment assay (Table 2). In the mini-G protein recruitment assay at the gpH 2 R, 20−25 were strong partial agonists with slightly increased potencies.…”

Section: ■ Results and Discussionsupporting

confidence: 75%

Discovery of a G Protein-Biased Radioligand for the Histamine H₂ Receptor with Reversible Binding Properties

et al. 2020

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Currently employed histamine H2 receptor (H2R) radioligands possess several drawbacks, for example, high non-specificity, insurmountable binding, or short half-life. We report the synthesis and the chemical and pharmacological characterization of the highly stable carbamoylguanidine-type radioligand [3H]UR-KAT479 ([3H]23), a subtype selective histamine H2 receptor G protein-biased agonist. [3H]23 was characterized by saturation, kinetic, and competition binding assays at the human, guinea pig, and mouse H2 receptors (co-)expressed in HEK293(T) cells. [3H]23 reversibly bound to the respective H2Rs with moderate to high affinity (human/guinea pig/mouse K d: 24/28/94 nM). In order to investigate the applicability of carbamoylguanidine-type ligands in animal studies elucidating the role of the H2R in the brain, we performed a preliminary partitioning experiment in the whole human/mouse blood, which indicated a low binding of [3H]23 to red blood cells. These properties turn [3H]23 into a powerful tool for the determination of binding affinities and demonstrate the promising pharmacokinetic profile of carbamoylguanidine-type ligands.

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Section: ■ Results and Discussionsupporting

confidence: 75%

Discovery of a G Protein-Biased Radioligand for the Histamine H₂ Receptor with Reversible Binding Properties

et al. 2020

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Histamine H2 Receptor Biased Signaling Methods

Cited by 1 publication

References 140 publications

Discovery of a G Protein-Biased Radioligand for the Histamine H₂ Receptor with Reversible Binding Properties

Discovery of a G Protein-Biased Radioligand for the Histamine H₂ Receptor with Reversible Binding Properties

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Histamine H2 Receptor Biased Signaling Methods

Cited by 1 publication

References 140 publications

Discovery of a G Protein-Biased Radioligand for the Histamine H2 Receptor with Reversible Binding Properties

Discovery of a G Protein-Biased Radioligand for the Histamine H2 Receptor with Reversible Binding Properties

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Discovery of a G Protein-Biased Radioligand for the Histamine H₂ Receptor with Reversible Binding Properties

Discovery of a G Protein-Biased Radioligand for the Histamine H₂ Receptor with Reversible Binding Properties