ArticleCirculation research2008
Nuclear alpha1-adrenergic receptors signal activated ERK localization to caveolae in adult cardiac myocytes.
Article in Circulation research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 124 citations in OpenAlex.
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- Mechanisms of Location Bias in G Protein-Coupled Receptors.Handbook of experimental pharmacology · 2026Review
- Unique Role of Intracellular Perinuclear βCirculation · 2025Article
- Polynorepinephrine nanoparticles activate vascular smooth muscle alpha-1 adrenergic receptors.Nanoscale advances · 2025Article
- Crhr1 and epinephrine utilize the central Ras-MAPK pathway in mediating the acute stress-related locomotor activity in zebrafish larvae.Frontiers in endocrinology · 2025Article
- Internalized β2-Adrenergic Receptors Oppose PLC-Dependent Hypertrophic Signaling.Circulation research · 2024Article
- G Protein-Coupled Receptors: A Century of Research and Discovery.Circulation research · 2024Review
- Exploring the Role of Non-synonymous and Deleterious Variants Identified in Colorectal Cancer: A Multi-dimensional Computational Scrutiny of Exomes.Current genomics · 2024Article
- Cardiac contraction and relaxation are regulated by distinct subcellular cAMP pools.Nature chemical biology · 2024Article
- Signalling of Adrenoceptors: Canonical Pathways and New Paradigms.Handbook of experimental pharmacology · 2024Review
- Recent advances on the role of monoamine oxidases in cardiac pathophysiology.Basic research in cardiology · 2023Article
- Nuclear Calcium in Cardiac (Patho)Physiology: Small Compartment, Big Impact.Biomedicines · 2023Review
- A Review of the Mechanism of Action of Drugs Used in Congestive Heart Failure in Pediatrics.Cureus · 2023Review
- α1-adrenergic receptors accompanied by GATA4 expression are related to proarrhythmic conduction and automaticity in rat interatrial septum.Journal of physiology and biochemistry · 2022Article
- GPCRs in Intracellular Compartments: New Targets for Drug Discovery.Biomolecules · 2022Review
- Norepinephrine activates βGlia · 2022Article
- Genome-Wide DNA Methylation Patterns of Muscle and Tail-Fat in DairyMeade Sheep and Mongolian Sheep.Animals : an open access journal from MDPI · 2022Article
- Review
- Subcellular Propagation of Cardiomyocyte β-Adrenergic Activation of Calcium Uptake Involves Internal β-Receptors and AKAP7.Function (Oxford, England) · 2022Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
We previously identified an alpha1-AR-ERK (alpha1A-adrenergic receptor-extracellular signal-regulated kinase) survival signaling pathway in adult cardiac myocytes. Here, we investigated localization of alpha1-AR subtypes (alpha1A and alpha1B) and how their localization influences alpha1-AR signaling in cardiac myocytes. Using binding assays on myocyte subcellular fractions or a fluorescent alpha1-AR antagonist, we localized endogenous alpha1-ARs to the nucleus in wild-type adult cardiac myocytes. To clarify alpha1 subtype localization, we reconstituted alpha1 signaling in cultured alpha1A- and alpha1B-AR double knockout cardiac myocytes using alpha1-AR-green fluorescent protein (GFP) fusion proteins. Similar to endogenous alpha1-ARs and alpha1A- and alpha1B-GFP colocalized with LAP2 at the nuclear membrane. alpha1-AR nuclear localization was confirmed in vivo using alpha1-AR-GFP transgenic mice. The alpha1-signaling partners Galphaq and phospholipase Cbeta1 also colocalized with alpha1-ARs only at the nuclear membrane. Furthermore, we observed rapid catecholamine uptake mediated by norepinephrine-uptake-2 and found that alpha1-mediated activation of ERK was not inhibited by a membrane impermeant alpha1-blocker, suggesting alpha1 signaling is initiated at the nucleus. Contrary to prior studies, we did not observe alpha1-AR localization to caveolae, but we found that alpha1-AR signaling initiated at the nucleus led to activated ERK localized to caveolae. In summary, our results show that nuclear alpha1-ARs transduce signals to caveolae at the plasma membrane in cardiac myocytes.
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Registered trials
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