Repetitive treatment with serotonin induces changes in protein synthesis and protein phosphorylation in the CNS of the leech Hirudo medicinalis

Many neural functions are regulated by phosphorylation of proteins. In the leech, behavioral experiments have shown that SHT is involved in short-term non-associative learning through the activation of cAMP- dependent protein kinases. On the other hand, long term dishabituation requires new protein synthesis but the mechanisms underlying the passage from the short-term to the long-term learning are unknown. In order to study this issue, we have labeled ganglia with either (32P)- orthophosphoric add or (35S)-methionine. Labeled proteins were separated by bidimensional electrophoresis and detected by autoradiography. A single treatment with 5HT 5OµM was found to produce a general increase in protein phosphorylation. Repetitive treatments with 5HT induced a higher level of protein phosphorylation and a modification of (35)-methionine incorporation. Repetitive treatment with ooth 5HT and the protein kinase inhibitor staurosporine resulted in a 20-5O% inhibition of (35S)-methionine incorporation into proteins. These results suggest that protein phosphorylation is important to trigger protein synthesis, possibily mediating the passage from short-term to long-tenn modulation.