Expression of CYP 4A ω-hydroxylase and formation of 20-hydroxyeicosatetreanoic acid (20-HETE) in cultured rat brain astrocytes
| Autor: | David X. Zhang, Debebe Gebremedhin, Koryn A. Carver, David R. Harder, Nicole Rau, Kevin R. Rarick, Richard J. Roman |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Epoxygenase medicine.medical_specialty Physiology Stimulation Vasodilation Biology Receptors Metabotropic Glutamate Biochemistry Article Gene Expression Regulation Enzymologic Muscle Smooth Vascular 03 medical and health sciences chemistry.chemical_compound Cerebral circulation 0302 clinical medicine Cytochrome P-450 Enzyme System Internal medicine Hydroxyeicosatetraenoic Acids medicine Myocyte Animals Pharmacology Arachidonic Acid Brain Cell Biology Rats 030104 developmental biology medicine.anatomical_structure Endocrinology chemistry Metabotropic glutamate receptor Astrocytes Cerebrovascular Circulation biology.protein cardiovascular system Arachidonic acid lipids (amino acids peptides and proteins) 030217 neurology & neurosurgery Astrocyte |
| Popis: | Astrocytes secrete vasodilator and vasoconstrictor factors via end feet processes, altering blood flow to meet neuronal metabolic demand. Compared to what is known about the ability of astrocytes to release factors that dilate local cerebral vasculature, very little is known regarding the source and identity of astrocyte derived constricting factors. The present study investigated if astrocytes express CYP 4A ω-hydroxylase and metabolize arachidonic acid (AA) to 20-hydroxyeicotetraenoic acid (20-HETE) that regulates KCa channel activity in astrocytes and cerebral arterial myocyte contractility. Here we report that cultured astrocytes express CYP 4A2/3 ω-hydroxylase mRNA and CYP 4A protein and produce 20-HETE and the CYP epoxygenase metabolites epoxyeicosatrienoic acids (EETs) when incubated with AA. The production of 20-HETE and EETs was enhanced following stimulation of metabotropic glutamate receptors (mGluR) on the astrocytes. Exogenous application of 20-HETE attenuated, whereas inhibition of 20-HETE production with HET-0016 increased the open state probabilities (NPo) of 71 pS and 161 pS KCa single-channel currents recorded from astrocytes. Exposure of isolated cerebral arterial myocytes to conditioned media from cultured astrocytes caused shortening of the length of freshly isolated cerebral arterial myocytes that was not evident following inhibition of astrocyte 20-HETE synthesis and action. These findings suggest that astrocytes not only release vasodilator EETs in response to mGluR stimulation but also synthetize and release the cerebral arterial myocyte constrictor 20-HETE that also functions as an endogenous inhibitor of the activity of two types of KCa channel currents found in astrocytes. |
| Databáze: | OpenAIRE |
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