Cyclic AMP stimulates serotonin N-acetyltransferase activity in Xenopus retina in vitro

The possible involvement of cyclic AMP in the regulation of retinal serotonin N-acetyltransferase (NAT) activity was investigated using eye cups of Xenopus laevis cultured in a defined medium. Addition of dibutyrylcyclic AMP (dbcAMP) increased retinal NAT activity in eye cups cultured in light. Addition of adenosine or 5'-AMP under identical conditions was without effect. 3-Isobutylmethylxanthine (IBMX) increased both retinal cyclic AMP levels and NAT activity in light-exposed eye cups. Forskolin also increased the concentration of cyclic AMP and the activity of NAT, and the effect of forskolin on both of these parameters was synergistically enhanced by IBMX. The effects of forskolin and of dbcAMP did not require the addition of calcium to the medium; thus, Ca2+ -dependent synaptic transmission does not appear to be required for the response to these drugs. Incubation conditions that activate cyclic AMP-dependent protein kinase in retinal homogenates had no effect on NAT activity, suggesting that direct phosphorylation of NAT was probably not involved in the response to elevating cyclic AMP in situ. The effect of dbcAMP was blocked by protein synthesis inhibitors. These results suggest that cyclic AMP increases retinal NAT activity by a mechanism that involves protein synthesis, and support a role for cyclic AMP in the nocturnal increase of NAT activity in darkness.