ArticleCommunications biology2021
CGRP, adrenomedullin and adrenomedullin 2 display endogenous GPCR agonist bias in primary human cardiovascular cells.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
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- Single-Nucleus Multi-Omics Reveals Hypoxia-Driven Angiogenic Programs and Their Epigenetic Control in Sinonasal Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CGRP: the immune system's double agent - context-dependent roles in inflammation, resolution and cancer.Frontiers in immunology · 2026Review
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Receptor activity-modifying protein 3 enhances GLP-1-mediated insulin secretion.The Journal of biological chemistry · 2025Article
- Ubrogepant, erenumab, and eptinezumab antagonize positive inotropic effects of the calcitonin gene-related peptide in the isolated human atrium.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Research progress on the correlation between corneal neovascularization and lymphangiogenesis (Review).Molecular medicine reports · 2025Review
- Quantitative approaches for studying G protein-coupled receptor signalling and pharmacology.Journal of cell science · 2025Review
- Unraveling the role of GPCR signaling in metabolic reprogramming and immune microenvironment of lung adenocarcinoma: a multi-omics study with experimental validation.Frontiers in immunology · 2025Article
- Quantitative proteomics reveals CLR interactome in primary human cells.The Journal of biological chemistry · 2024Article
- Variable CGRP family peptide signaling durations and the structural determinants thereof.Biochemical pharmacology · 2024Article
- New Insights into the Structure and Function of Class B1 GPCRs.Endocrine reviews · 2023Article
- Clinical Potential of Adrenomedullin Signaling in the Cardiovascular System.Circulation research · 2023Review
- Shared and independent roles of CGRP and PACAP in migraine pathophysiology.The journal of headache and pain · 2023Review
- CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond.Physiological reviews · 2023Review
- Adrenomedullin 2/intermedin is a slow off-rate, long-acting endogenous agonist of the adrenomedullinbioRxiv : the preprint server for biology · 2023Article
- Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins.Pharmacological reviews · 2023Review
- The vascular role of CGRP: a systematic review of human studies.Frontiers in neurology · 2023Review
- Elucidating the Ability of CGRP to Modulate Microvascular Events in Mouse Skin.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Agonist bias occurs when different ligands produce distinct signalling outputs when acting at the same receptor. However, its physiological relevance is not always clear. Using primary human cells and gene editing techniques, we demonstrate endogenous agonist bias with physiological consequences for the calcitonin receptor-like receptor, CLR. By switching the receptor-activity modifying protein (RAMP) associated with CLR we can "re-route" the physiological pathways activated by endogenous agonists calcitonin gene-related peptide (CGRP), adrenomedullin (AM) and adrenomedullin 2 (AM2). AM2 promotes calcium-mediated nitric oxide signalling whereas CGRP and AM show pro-proliferative effects in cardiovascular cells, thus providing a rationale for the expression of the three peptides. CLR-based agonist bias occurs naturally in human cells and has a fundamental purpose for its existence. We anticipate this will be a starting point for more studies into RAMP function in native environments and their importance in endogenous GPCR signalling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.