Role of Prostanoid Receptors in the Inhibitory Effect of Synthetic Isoprostanes on Potassium‐Induced [ 3 H]D‐Aspartate Release in Isolated Bovine Retina

We investigated the role of prostanoid receptors in the inhibitory effect of synthetic isoprostane epimers, AG113A and B on K + ‐induced glutamate release (using [ 3 H]D‐aspartate as a marker) in isolated bovine retina. Isolated neural retinae were incubated in oxygenated Krebs solution containing 200nM of [ 3 H]D‐aspartate for 60 mins and then prepared for studies of neurotransmitter release using the superfusion method. Release of [ 3 H]D‐aspartate was evoked by iso‐osmotic concentration of K + (50mM)‐stimuli applied at 80–88 mins(S 1 ) and 116–124 mins(S 2 ) after the onset of superfusion. Both AG113A and B attenuated K + ‐induced [ 3 H]D‐aspartate release from retina without affecting basal tritium overflow. AG113A exhibited a biphasic response, with the maximal inhibitory effect of 36%(n=7;p<0.001) being achieved at 0.01ìM while AG113B achieved a maximal inhibitory effect of 26%(n=3;p<0.01) at the 0.1ìM concentration of the isoprostane. The prostanoid antagonists, AH608(EP1‐3/DP1), BAY‐u3405(DP2) and AH23848(EP4) did not reverse the inhibitory effect of AG113A on K + ‐induced D‐aspartate release. EP1 antagonists, SC19220 and SC1322 completely reversed the inhibitory effect of AG113A on the neurotransmitter release. Prostanoid EP1‐receptors mediate the inhibitory effect of AG113 on K + ‐evoked [ 3 H]D‐aspartate release in isolated bovine retinae.