Dual effect of isoprostanes on the release of [3H]D-aspartate from isolated bovine retinae: role of arachidonic acid metabolites

The effect of 8-isoprostanes on potassium (K+)-depolarization-evoked release of [3H]D-aspartate from bovine isolated retinae was investigated. Isolated bovine retinae were prepared for studies of K(+)-evoked release of [3H]D-aspartate using the Superfusion Method. Low concentrations of 8-isoPGF(2alpha) (1-100 nM) inhibited whereas higher concentrations of this 8-isoprostane (100 nM-30 microM) enhanced K(+)-induced [3H]D-aspartate overflow. The excitatory effect of 8-isoPGF(2alpha) was mimicked by thromboxane receptor agonist, U-46619 and blocked by thromboxane receptor antagonist, SQ 29,548 (10 microM). Pretreatment of tissues with the cyclooxygenase (COX) inhibitor, flurbiprofen unmasked an inhibitory effect of high concentrations of 8-isoPGF(2alpha) (1-30 microM) on [3H]D-aspartate release that was attenuated by AH 6809 (10 microM). In conclusion, 8-isoPGF(2alpha) exhibits a dual regulatory effect on K(+)-induced [3H]D-aspartate release in isolated bovine retinae. The inhibitory action caused by 8-isoPGF(2alpha) is due to the activation of EP1/EP2 receptors while the excitatory effects are due to the activation of thromboxane receptors.