Antinociception Produced by 14,15-Epoxyeicosatrienoic Acid Is Mediated by the Activation of β-Endorphin and Met-Enkephalin in the Rat Ventrolateral Periaqueductal Gray

摘要: Cytochrome P450 genes catalyze formation of epoxyeicosatrienoic acids (EETs) from arachidonic acid. The effects 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET microinjected into the ventrolateral periaqueductal gray (vlPAG) on thermally produced tail-flick response were studied in male Sprague-Dawley rats. vlPAG (3–156 pmol) dose-dependently inhibited (ED50 = 32.5 pmol). In contrast, 11,12-EET at a dose 156 pmol not active when injected vlPAG. failed to displace radiobinding [3H][d-Ala2,NHPe4, Gly-ol5]enkephalin (μ-opioid receptor ligand) or [3H]naltrindole (δ-opioid crude membrane fractions rat brain. Tail-flick inhibition by was blocked intra-vlPAG pretreatment with antiserum against β-endorphin Met-enkephalin μ-opioid antagonist d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) δ-opioid naltrindole but dynorphin A[1–17] κ-opioid nor-binaltorphimine. addition, treatment intrathecal antiserum, naltrindole, CTOP antiserum. It is concluded that 1) itself does have any affinity for μ- receptors 2) activates Met-enkephalin, which subsequently act μ-and produce antinociception.