G Protein–Coupled Receptors in Asthma Therapy: Pharmacology and Drug Action

Wendell, Stacy G.; Fan, Hao; Zhang, Cheng

doi:10.1124/pr.118.016899

Cited by 81 publications

(66 citation statements)

References 674 publications

(719 reference statements)

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“…To date, numerous clinical trials have shown that DP2 antagonists are effective for patients with asthma ( Figure 1) [153][154][155]. Fevipiprant (QAW039), an oral DP2 antagonist, improved pulmonary function in asthmatic patients with severely impaired lung functions and patients with uncontrolled asthma using an inhaled corticosteroid (ICS) [132,133,156].…”

Section: Asthmamentioning

confidence: 99%

The Biology of Prostaglandins and Their Role as a Target for Allergic Airway Disease Therapy

Lee

Kim

2020

IJMS

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Prostaglandins (PGs) are a family of lipid compounds that are derived from arachidonic acid via the cyclooxygenase pathway, and consist of PGD 2 , PGI 2 , PGE 2 , PGF 2 , and thromboxane B 2 . PGs signal through G-protein coupled receptors, and individual PGs affect allergic inflammation through different mechanisms according to the receptors with which they are associated. In this review article, we have focused on the metabolism of the cyclooxygenase pathway, and the distinct biological effect of each PG type on various cell types involved in allergic airway diseases, including asthma, allergic rhinitis, nasal polyposis, and aspirin-exacerbated respiratory disease.

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Section: Asthmamentioning

confidence: 99%

The Biology of Prostaglandins and Their Role as a Target for Allergic Airway Disease Therapy

Lee

Kim

2020

IJMS

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“…β-adrenergic receptors (β-ARs) are the most structurally and pharmacologically studied subgroup of GPCRs [ 15 , 16 ]. They are also important drug targets, where both beta- mimetics and beta-blockers are employed in therapies of various conditions [ 17 , 18 , 19 ]. One of the first structurally evident instances of biased agonism at the β-AR system was characterized for bucindolol, carvedilol and nebivolol.…”

Section: β-Adrenergic Receptorsmentioning

confidence: 99%

Structural Insights into Ligand—Receptor Interactions Involved in Biased Agonism of G-Protein Coupled Receptors

Jóźwiak

Płazińska

2021

Molecules

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G protein-coupled receptors (GPCRs) are versatile signaling proteins that mediate complex cellular responses to hormones and neurotransmitters. Ligand directed signaling is observed when agonists, upon binding to the same receptor, trigger significantly different configuration of intracellular events. The current work reviews the structurally defined ligand – receptor interactions that can be related to specific molecular mechanisms of ligand directed signaling across different receptors belonging to class A of GPCRs. Recent advances in GPCR structural biology allow for mapping receptors’ binding sites with residues particularly important in recognition of ligands’ structural features that are responsible for biased signaling. Various studies show particular role of specific residues lining the extended ligand binding domains, biased agonists may alternatively affect their interhelical interactions and flexibility what can be translated into intracellular loop rearrangements. Studies on opioid and angiotensin receptors indicate importance of residues located deeper within the binding cavity and direct interactions with receptor residues linking the ortosteric ligand binding site with the intracellular transducer binding domain. Collection of results across different receptors may suggest elements of common molecular mechanisms which are responsible for passing alternative signals from biased agonists.

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“…In the context of the recent COVID-19 pandemic, Zhou et al [7] suggested that angiotensin receptor blockers may have the potential of inhibiting viral entry and can be considered as a prospective repurposable drug for 2019-nCoV/SARS-CoV-2. Many therapeutics used to either enhance bronchodilation or prevent bronchoconstriction for treating respiratory diseases including asthma are known to target β 2 -adrenergic receptors [8,9] and modulate Ca 2+ -signaling [10]. In this context, a more profound knowledge of the role and mechanism through which cytosolic Ca 2+ is regulated by GPCRs can help in curing these diseases.…”

Section: Introductionmentioning

confidence: 99%

GPCR mediated control of calcium dynamics: A systems perspective

Dhyani

Gare

Gupta

et al. 2020

Cellular Signalling

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G-protein coupled receptor (GPCR) mediated calcium (Ca 2+)-signaling transduction remains crucial in designing drugs for various complex diseases including neurodegeneration, chronic heart failure as well as respiratory diseases. Although there are several reviews detailing various aspects of Ca 2+-signaling such as the role of IP 3 receptors and Ca 2+-induced-Ca 2+-release, none of them provide an integrated view of the mathematical descriptions of GPCR signal transduction and investigations on dose-response curves. This article is the first study in reviewing the network structures underlying GPCR signal transduction that control downstream [Ca c 2+ ]oscillations. The central theme of this paper is to present the biochemical pathways, as well as molecular mechanisms underlying the GPCR-mediated Ca 2+-dynamics in order to facilitate a better understanding of how agonist concentration is encoded in Ca 2+-signals for G αq , G αs , and G αi/o signaling pathways. Moreover, we present the GPCR targeting drugs that are relevant for treating cardiac, respiratory, and neuro-diseases. The current paper presents the ODE formulation for various models along with the detailed schematics of signaling networks. To provide a systems perspective, we present the network motifs that can provide readers an insight into the complex and intriguing science of agonist-mediated Ca 2+-dynamics. One of the features of this review is to pinpoint the interplay between positive and negative feedback loops that are involved in controlling intracellular [Ca c 2+ ]-oscillations. Furthermore, we review several examples of dose-response curves obtained from [Ca c 2+ ]-spiking for various GPCR pathways. This paper is expected to be useful for pharmacologists and computational biologists for designing clinical applications of GPCR targeting drugs through modulation of Ca 2+dynamics.

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G Protein–Coupled Receptors in Asthma Therapy: Pharmacology and Drug Action

Abstract: Wendell et al.

Cited by 81 publications

References 674 publications

The Biology of Prostaglandins and Their Role as a Target for Allergic Airway Disease Therapy

The Biology of Prostaglandins and Their Role as a Target for Allergic Airway Disease Therapy

Structural Insights into Ligand—Receptor Interactions Involved in Biased Agonism of G-Protein Coupled Receptors

GPCR mediated control of calcium dynamics: A systems perspective

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