Formation, Metabolism, and Action of Hepoxilin A3in the Rat Pineal Gland
| Autor: | Cecil R. Pace-Asciak, Abdallah Gharib, Nicole Sarda, Isabelle Delton, Michel Lagarde, Denis Reynaud |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Adenosine 4 5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine Adenosine-5'-(N-ethylcarboxamide) Tritium Pineal Gland Biochemistry Gas Chromatography-Mass Spectrometry Rats Sprague-Dawley Cellular and Molecular Neuroscience chemistry.chemical_compound Lipoxygenase Pineal gland 8 11 14-Eicosatrienoic Acid Hepoxilin-epoxide hydrolase Cyclic AMP medicine Animals Rats Wistar Cells Cultured Arachidonic Acid biology Metabolism Adenosine receptor Rats medicine.anatomical_structure chemistry Hepoxilin biology.protein Arachidonic acid Endocrine gland |
| Zdroj: | Journal of Neurochemistry. 62:126-133 |
| ISSN: | 1471-4159 0022-3042 |
| DOI: | 10.1046/j.1471-4159.1994.62010126.x |
| Popis: | The present study was undertaken to investigate the possible formation of hepoxilin A3 in the rat pineal gland and to study the potential physiological role for this compound in this tissue. Incubation of homogenates of rat pineal glands with arachidonic acid (66 microM) led to the appearance of hepoxilin A3 (HxA3) analyzed as its stable trihydroxy derivative, trioxilin A3 by gas chromatography in both the electron impact and negative ion chemical ionization modes. Endogenous formation of HxA3 is estimated to be 1.43 +/- 0.66 ng/micrograms of protein. This amount is not modified when the tissue is boiled (2.07 +/- 0.66 ng/micrograms of protein). However, the formation of this compound was stimulated to 21.26 +/- 5.82 ng/micrograms of protein when exogenous arachidonic acid was added to the homogenate. Addition of the dual cyclooxygenase/lipoxygenase inhibitor BW 755C (10 micrograms) resulted in a partial blockade of hepoxilin formation. Using [1-14C]HxA3, we demonstrated that the pineal gland contained hepoxilin epoxide hydrolase, which hydrolyzed HxA3 into trioxilin A3. This hydrolysis was inhibited by 1 mumol/L of 3,3,3-trichloropropene-1,2-oxide. In a separate study, HxA3 in the presence of 3,3,3-trichloropropene-1,2-oxide to block the hydrolysis of HxA3 decreased the production of cyclic AMP in cultured organ rat pineals after stimulation with 5'-N-ethylcarboxamidoadenosine, an A1/A2 adenosine receptor agonist. This effect is stereospecific because the (8S)-enantiomer is more active in decreasing cyclic AMP production (-88.7%) than the (8R)-enantiomer. This is the first demonstration of the presence, metabolism, and action of HxA3 in the rat pineal gland. |
| Databáze: | OpenAIRE |
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