Epinephrine modulates Na+/K+ ATPase activity in Caco-2 cells via Src, p38MAPK, ERK and PGE2
| Autor: | Sawsan Ibrahim Kreydiyyeh, Layla El Moussawi, Mohamed Chakkour |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adenosine Triphosphatase
0301 basic medicine MAPK/ERK pathway Prostaglandin Cell Lines Adrenergic lcsh:Medicine Biochemistry p38 Mitogen-Activated Protein Kinases Ouabain Colorimetric Protein Concentration Assays Catecholamines 0302 clinical medicine Medicine and Health Sciences Lipid Hormones Amines Post-Translational Modification Phosphorylation Receptor lcsh:Science Multidisciplinary Organic Compounds Chemistry Neurochemistry Neurotransmitters Adrenergic alpha-2 Receptor Antagonists Enzymes Bioassays and Physiological Analysis src-Family Kinases Epinephrine Physical Sciences Biological Cultures Anatomy Sodium-Potassium-Exchanging ATPase Research Article Signal Transduction medicine.drug Biogenic Amines medicine.medical_specialty Colon MAP Kinase Signaling System Research and Analysis Methods Dinoprostone 03 medical and health sciences Receptors Adrenergic alpha-2 Internal medicine Protein Concentration Assays medicine Adrenergic antagonist Humans Molecular Biology Techniques Colorimetric Assays Molecular Biology Protein Kinase Inhibitors Ion transporter Molecular Biology Assays and Analysis Techniques Organic Chemistry lcsh:R Chemical Compounds Phosphatases Biology and Life Sciences Proteins Cell Biology Hormones Gastrointestinal Tract 030104 developmental biology Endocrinology Enzymology lcsh:Q Caco-2 Cells Biochemical Analysis Digestive System 030217 neurology & neurosurgery Neuroscience Adrenergic Signal Transduction |
| Zdroj: | PLoS ONE, Vol 13, Iss 2, p e0193139 (2018) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Epinephrine, a key stress hormone, is known to affect ion transport in the colon. Stress has been associated with alterations in colonic functions leading to changes in water movements manifested as diarrhea or constipation. Colonic water movement is driven by the Na+-gradient created by the Na+/K+-ATPase. Whether epinephrine acts via an effect on the Na+/K+-ATPase hasn't been studied before. The aim of this work was to investigate the effect of epinephrine on the Na+/K+-ATPase and to elucidate the signaling pathway involved using CaCo-2 cells as a model. The activity of the Na+/K+-ATPase was assayed by measuring the amount of inorganic phosphate released in presence and absence of ouabain, a specific inhibitor of the enzyme. Epinephrine, added for 20 minutes, decreased the activity of the Na+/K+-ATPase by around 50%. This effect was found to be mediated by α2 adrenergic receptors as it was fully abolished in the presence of yohimbine an α2-blocker, but persisted in presence of other adrenergic antagonists. Furthermore, treatment with Rp-cAMP, a PKA inhibitor, mimicked epinephrine's negative effect and didn't result in any additional inhibition when both were added simultaneously. Treatment with indomethacin, PP2, SB202190, and PD98059, respective inhibitors of COX enzymes, Src, p38MAPK, and ERK completely abrogated the effect of epinephrine. The effect of epinephrine did not appear also in presence of inhibitors of all four different types of PGE2 receptors. Western blot analysis revealed an epinephrine-induced increase in the phosphorylation of p38 MAPK and ERK that disappeared in presence of respectively PP2 and SB2020190. In addition, an inhibitory effect, similar to that of epinephrine's, was observed upon incubation with PGE2. It was concluded that epinephrine inhibits the Na+/K+-ATPase by the sequential activation of α2 adrenergic receptors, Src, p38MAPK, and ERK leading to PGE2 release. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|