Light-adaptation attenuates the effects of phosphodiesterase blackade by Zaprinast in the isolated rat retina.

The effect of the type V/VI-selective phosphodiesterase inhibitor, Zaprinast, (200 microM) on the light-evoked extracellular field potential (EFP) in the isolated rat retina was tested under dark- and light-adapted conditions at two different temperatures. Peak enhancement EFP in dark- (344 +/- 70%; mean +/- SEM) and light-adapted (182 +/- 31%) retina at 37 degrees C was reached within 3 min of treatment with Zaprinast (200 microM) followed by a slower decrease to a level of 85 +/- 14 and 26 +/- 7% in dark- and light-adapted retina, respectively. The effect of Zaprinast (20 microM) on the pharmacologically-isolated photoreceptor component of the EFP was lost with increasing levels of background light. This may suggest that there is a slow time scale (minutes) shift in the steady state level of cGMP during light-adaptation.