ArticlePloS one2009
Metabolites of an Epac-selective cAMP analog induce cortisol synthesis by adrenocortical cells through a cAMP-independent pathway.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 30 citations in OpenAlex.
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Selective small-molecule EPAC activators.Biochemical Society transactions · 2019Review
- Evidence in Favor of an Alternative Glucocorticoid Synthesis Pathway During Acute Experimental Chagas Disease.Frontiers in endocrinology · 2019Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Role of EPAC in cAMP-Mediated Actions in Adrenocortical Cells.Frontiers in endocrinology · 2016Review
- Cyclic AMP sensor EPAC proteins and energy homeostasis.Trends in endocrinology and metabolism: TEM · 2014Review
- Article
- Role of guanine-nucleotide exchange factor Epac in renal physiology and pathophysiology.American journal of physiology. Renal physiology · 2013Review
- Enhanced leptin sensitivity, reduced adiposity, and improved glucose homeostasis in mice lacking exchange protein directly activated by cyclic AMP isoform 1.Molecular and cellular biology · 2013Article
- β-Adrenergic receptors stimulate interleukin-6 production through Epac-dependent activation of PKCδ/p38 MAPK signalling in neonatal mouse cardiac fibroblasts.British journal of pharmacology · 2012Article
- 8-Phenylthio-adenines stimulate the expression of steroid hydroxylases, Cav3.2 Ca²⁺ channels, and cortisol synthesis by a cAMP-independent mechanism.American journal of physiology. Endocrinology and metabolism · 2011Article
- PKA and Epac synergistically inhibit smooth muscle cell proliferation.Journal of molecular and cellular cardiology · 2011Article
- ACTH induces Cav3.2 current and mRNA by cAMP-dependent and cAMP-independent mechanisms.The Journal of biological chemistry · 2010Article
- Role of the cAMP-binding protein Epac in cardiovascular physiology and pathophysiology.Pflugers Archiv : European journal of physiology · 2010Review
- cAMP analogs and their metabolites enhance TREK-1 mRNA and K+ current expression in adrenocortical cells.Molecular pharmacology · 2010Article
- Inhibition of the equilibrative nucleoside transporter 1 and activation of A2A adenosine receptors by 8-(4-chlorophenylthio)-modified cAMP analogs and their hydrolytic products.The Journal of biological chemistry · 2009Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Adrenal zona fasciculata (AZF) cells express a cAMP-activated guanine nucleotide exchange protein (Epac2) that may function in ACTH-stimulated cortisol synthesis. Experiments were done to determine whether cAMP analogs that selectively activate Epacs could induce cortisol synthesis and the expression of genes coding for steroidogenic proteins in bovine AZF cells. Treatment of AZF cells with the Epac-selective cAMP analog (ESCA) 8CPT-2'-OMe-cAMP induced large (>100 fold), concentration-dependent, delayed increases in cortisol synthesis and the expression of mRNAs coding for the steroid hydroxylases CYP11a1, CYP17, CYP21, and the steroid acute regulatory protein (StAR). However, a non-hydrolyzable analog of this ESCA, Sp-8CPT-2'-OMe-cAMP, failed to stimulate cortisol production even at concentrations that activated Rap1, a downstream effector of Epac2. Accordingly, putative metabolites of 8CPT-2'-OMe-cAMP, including 8CPT-2'-OMe-5'AMP, 8CPT-2'-OMe-adenosine, and 8CPT-adenine all induced cortisol synthesis and steroid hydroxylase mRNA expression with a temporal pattern, potency, and effectiveness similar to the parent compound. At concentrations that markedly stimulated cortisol production, none of these metabolites significantly activated cAMP-dependent protein kinase (PKA). These results show that one or more metabolites of the ESCA 8CPT-2'-OMe-cAMP induce cortico-steroidogenesis by activating a panel of genes that code for steroidogenic proteins. The remarkable increases in cortisol synthesis observed in this study appear to be mediated by a novel cAMP-, Epac- and PKA-independent signaling 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.