ArticleJournal of cardiovascular pharmacology2013
Adenosine A1 receptors link to smooth muscle contraction via CYP4a, protein kinase C-α, and ERK1/2.
Article in Journal of cardiovascular pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Design, Synthesis and Biological Evaluation of 1,3,5-Triazine Derivatives Targeting hAMolecules (Basel, Switzerland) · 2022Article
- Adenosine AMolecular and cellular biochemistry · 2021Article
- Long-term adenosine A1 receptor activation-induced sortilin expression promotes α-synuclein upregulation in dopaminergic neurons.Neural regeneration research · 2020Article
- Ephx2-gene deletion affects acetylcholine-induced relaxation in angiotensin-II infused mice: role of nitric oxide and CYP-epoxygenases.Molecular and cellular biochemistry · 2020Article
- Purinergic Signaling During Hyperglycemia in Vascular Smooth Muscle Cells.Frontiers in endocrinology · 2020Review
- Regulation of Circadian Genes by the MAPK Pathway: Implications for Rapid Antidepressant Action.Neuroscience bulletin · 2020Review
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- Enhanced AEuropean journal of pharmacology · 2019Article
- Role of oxylipins in cardiovascular diseases.Acta pharmacologica Sinica · 2018Review
- Functional changes in vascular reactivity to adenosine receptor activation in type I diabetic mice.European journal of pharmacology · 2018Article
- Exploring Adenosine Receptor Ligands: Potential Role in the Treatment of Cardiovascular Diseases.Molecules (Basel, Switzerland) · 2017Review
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- Article
- Vascular endothelial over-expression of soluble epoxide hydrolase (Tie2-sEH) enhances adenosine AMolecular and cellular biochemistry · 2016Article
- Role of Adenosine Receptor(s) in the Control of Vascular Tone in the Mouse Pudendal Artery.The Journal of pharmacology and experimental therapeutics · 2016Article
- Angiotensin II stimulation alters vasomotor response to adenosine in mouse mesenteric artery: role for A1 and A2B adenosine receptors.British journal of pharmacology · 2015Article
- Transient postnatal fluoxetine decreases brain concentrations of 20-HETE and 15-epi-LXA4, arachidonic acid metabolites in adult mice.Prostaglandins, leukotrienes, and essential fatty acids · 2015Article
- Article
- Role of 20-HETE in the impaired myogenic and TGF responses of the Af-Art of Dahl salt-sensitive rats.American journal of physiology. Renal physiology · 2014Article
- Adenosine APhysiological reports · 2013Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Adenosine A1 receptor (A1AR) activation contracts smooth muscle, although signaling mechanisms are not thoroughly understood. Activation of A1AR leads to metabolism of arachidonic acid, including the production of 20-hydroxyeicosatetraenoic acid (20-HETE) by cytochrome P4504a (CYP4a). The 20-HETE can activate protein kinase C-α (PKC-α), which crosstalks with extracellular signal-regulated kinase (ERK1/2) pathway. Both these pathways can regulate smooth muscle contraction, we tested the hypothesis that A1AR contracts smooth muscle through a pathway involving CYP4a, PKC-α, and ERK1/2. Experiments included isometric tension recordings of aortic contraction and Western blots of signaling molecules in wild type (WT) and A1AR knockout (A1KO) mice. Contraction to the A1-selective agonist 2-chloro-N cyclopentyladenosine (CCPA) was absent in A1KO mice aortae, indicating the contractile role of A1AR. Inhibition of CYP4a (HET0016) abolished 2-chloro-N cyclopentyladenosine-induced contraction in WT aortae, indicating a critical role for 20-HETE. Both WT and A1KO mice aortae contracted in response to exogenous 20-HETE. Inhibition of PKC-α (Gö6976) or ERK1/2 (PD98059) attenuated 20-HETE-induced contraction equally, suggesting that ERK1/2 is downstream of PKC-α. Contractions to exogenous 20-HETE were significantly less in A1KO mice; reduced protein levels of PKC-α, p-ERK1/2, and total ERK1/2 supported this observation. Our data indicate that A1AR mediates smooth muscle contraction via CYP4a and a PKC-α-ERK1/2 pathway.
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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.