Regulation of K + ‐induced [ 3 H]D‐Aspartate Release by Synthetic Neuroprostanes in Isolated Bovine Retina

Neuroprostanes (nPs) are a series of isoprostane‐like compounds that are spontaneously derived by free‐radical catalyzed peroxidation of the polyunsaturated fatty acid, docosahexanoic acid. Although nPs are elevated in neurodegenerative conditions ( Musiek et al., Brain Pathol. 15:149,200 5), their biological effects remain largely unknown. We investigated the role of synthetic nPs, CO5‐667, CO5‐668 and CO5‐738 on K + ‐induced glutamate release (using [ 3 H]D‐aspartate as a marker) in isolated bovine retina. Isolated neural retina were incubated in oxygenated Krebs solution containing 200nM of [ 3 H] D‐aspartame 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. In the concentration range, 1 nM to 10 μM, the nPs enhanced K + ‐induced [ 3 H]D‐aspartate release from retina without affecting basal tritium overflow. For instance, C05‐668 achieved a maximal excitatory response of about 80% (p<0.01, n=4) at the 10 nM concentration of the nP. At an equimolar concentration of 10 nM, the rank order of activity was as follows: CO5‐668> CO5‐738> CO5‐667. In conclusion, the novel synthetic nPs exert an excitatory effect on K + ‐evoked [ 3 H]D‐aspartate release in isolated bovine retina.