ArticleMolecular pharmacology2010
cAMP analogs and their metabolites enhance TREK-1 mRNA and K+ current expression in adrenocortical cells.
Article in Molecular pharmacology, 2010. 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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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- The effect of wuling capsule on depression in Type 2 diabetic patients.Bioscience reports · 2020Trial
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Circadian photoperiod alters TREK-1 channel function and expression in dorsal raphe serotonergic neurons via melatonin receptor 1 signaling.Journal of pineal research · 2021Article
- Identification of Bioactive Chemical Markers inMolecules (Basel, Switzerland) · 2018Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Exchange proteins directly activated by cAMP (EPACs): Emerging therapeutic targets.Bioorganic & medicinal chemistry letters · 2017Review
- Cyclic AMP sensor EPAC proteins and energy homeostasis.Trends in endocrinology and metabolism: TEM · 2014Review
- TREK-1 currents in smooth muscle cells from pregnant human myometrium.American journal of physiology. Cell physiology · 2013Article
- Ca2+ and K+ channels of normal human adrenal zona fasciculata cells: properties and modulation by ACTH and AngII.The Journal of general physiology · 2013Article
- 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
- Protein kinase A and C regulate leak potassium currents in freshly isolated vascular myocytes from the aorta.PloS one · 2013Article
- Article
- Variants of stretch-activated two-pore potassium channel TREK-1 associated with preterm labor in humans.Biology of reproduction · 2012Article
- PKA and Epac synergistically inhibit smooth muscle cell proliferation.Journal of molecular and cellular cardiology · 2011Article
- Epac2-dependent mobilization of intracellular Ca²+ by glucagon-like peptide-1 receptor agonist exendin-4 is disrupted in β-cells of phospholipase C-ε knockout mice.The Journal of physiology · 2010Article
- ACTH induces Cav3.2 current and mRNA by cAMP-dependent and cAMP-independent mechanisms.The Journal of biological chemistry · 2010Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
bTREK-1 K(+) channels set the resting membrane potential of bovine adrenal zona fasciculata (AZF) cells and function pivotally in the physiology of cortisol secretion. Adrenocorticotropic hormone controls the function and expression of bTREK-1 channels through signaling mechanisms that may involve cAMP and downstream effectors including protein kinase A (PKA) and exchange protein 2 directly activated by cAMP (Epac2). Using patch-clamp and Northern blot analysis, we explored the regulation of bTREK-1 mRNA and K(+) current expression by cAMP analogs and several of their putative metabolites in bovine AZF cells. At concentrations sufficient to activate both PKA and Epac2, 8-bromoadenosine-cAMP enhanced the expression of both bTREK-1 mRNA and K(+) current. N(6)-Benzoyladenosine-cAMP, which activates PKA but not Epac, also enhanced the expression of bTREK-1 mRNA and K(+) current measured at times from 24 to 96 h. An Epac-selective cAMP analog, 8-(4-chlorophenylthio)-2'-O-methyl-cAMP (8CPT-2'-OMe-cAMP), potently stimulated bTREK-1 mRNA and K(+) current expression, whereas the nonhydrolyzable Epac activator 8-(4-chlorophenylthio)-2'-O-methyl-cAMP, Sp-isomer was ineffective. Metabolites of 8CPT-2'-OMe-cAMP, including 8-(4-chlorophenylthio)-2'-O-methyladenosine-5'-O-monophosphate and 8CPT-2'-OMe-adenosine, promoted the expression of bTREK-1 transcripts and ion current with a temporal pattern, potency, and effectiveness resembling that of the parent compound. Likewise, at low concentrations, 8-(4-chlorophenylthio)-cAMP (8CPT-cAMP; 30 microM) but not its nonhydrolyzable analog 8-(4-chlorophenylthio)-cAMP, Sp-isomer, enhanced the expression of bTREK-1 mRNA and current. 8CPT-cAMP metabolites, including 8CPT-adenosine and 8CPT-adenine, also increased bTREK-1 expression. These results indicate that cAMP increases the expression of bTREK-1 mRNA and K(+) current through a cAMP-dependent but Epac2-independent mechanism. They further demonstrate that one or more metabolites of 8-(4-chlorophenylthio)-cAMP analogs potently stimulate bTREK-1 expression by activation of a novel cAMP-independent mechanism. These findings raise significant questions regarding the specificity of 8-(4-chlorophenylthio)-cAMP analogs as cAMP mimetics.
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