Neuropeptide Y inhibits adenylyl cyclase activity in rabbit retina

Neuropeptide Y is known to be present in significant amounts in the retina of most vertebrates, but its physiological actions are largely unknown. We have therefore studied its effects on the intracellular cyclic AMP accumulation in rabbit retina. Neuropeptide Y had no effect on the basal cyclic AMP level but was found to inhibit the forskolin induced cyclic AMP accumulation. There were no differences between the effects of neuropeptide Y 1-36 and neuropeptide Y 13-36 (2.4 x 10(-6) M) suggesting the presence of the Y2 subtype of neuropeptide Y receptor. D-myo-inositol-1,2,6-trisphosphate, a novel neuropeptide Y-antagonist, reduced per se the forskolin induced cyclic AMP production. The pronounced inhibitory effect of neuropeptide Y on the forskolin induced cyclic AMP production was, on the other hand, totally abolished by D-myo-inositol-1,2,6-trisphosphate. The results indicate that neuropeptide Y acts on Y2 receptors in the retina to cause an inhibition of the adenylyl cyclase activity which could be antagonized by D-myo-inositol-1,2,6-trisphosphate. Such an inhibitory action of neuropeptide Y is similar to what has been found in brain tissue, but it has not previously been reported in the retina for neuropeptide Y or any of the other retinal neuropeptides.