Serotonin induces changes in protein phosphorylation and protein synthesis in the C.N.S. of Hirudo medicinalis

Serotonin (5HT) is involved in several behaviors of the leech, such as swimning, snortening and feeding. 1n addition, 5HT application mimicks elementary forms of non associative learning such as dishabituation. The role of 5HT on these short-term learning processes seems due to changes in phosphorylation of preexisting proteins. Since 5HT could mediate many of its functions through the activation of different protein kinases, we have compared the effect of 5HT on protein phosphorylation with those ones produced by activators of both protein kinase A or of protein kinase C. Phosphoproteins (PP) from different regions of the leech central nervous system (CNS) have been separated by means of two-dimensional electrophoresis and detected by autoradiography. Most of the PP are similarly distributed in segmental, cephalic and caudal ganglia. However, same regional differences do exist: in the chains of segmental ganglia, a group of phosphoproteins of 78 kDa and pI ; 6-6.5 is phosphorylated after treatment with 5HT, 8-Br-cAMP and dibutiryl phorbol ester; this group of PP is not detected either in caudal or in cephalic gangl~ion. From behavioural experiments cmerged the finding that new protein synthesis is needed for long-term learning. At the aim of studying the molecular mechanism underlying long-term learning, 35S-labeled ganglia have been stimulated repetitively with 50 uM 5HT. This treatment modifies the incorporation of (35S)-L-methionine into several proteins. Summing up, our data show that. 5HT, in the leech CNS, is ~apable of inducing phosphorylation of same proteins, but also of increasing protein synthesis.