CALMODULIN AND IN-VITRO REGENERATING FROG SCIATIC-NERVES - RELEASE AND EXTRACELLULAR EFFECTS

Although calmodulin (CaM) is commonly considered to be an intracellula r protein, it has been suggested lately that it is released and exerts functions extracellularly. In the present investigation this was stud ied in in vitro regenerating adult frog (Rana temporaria) sciatic nerv es. Using a multi-compartment incubation chamber, the non-neuronal cel ls in the outgrowth region of such nerves were radiolabelled with amin o acid precursors. Based on immunological criteria, these cells were s hown to release CaM. When the nerves were treated with CaM, both the o utgrowth of sensory axons and the injury-induced proliferation of non- neuronal cells were partially inhibited. The inhibitory effects occurr ed even when the incubation medium contained as little as 30 pM CaM. F urthermore, treatment with anti-CaM antibodies resulted in reduced out growth, which suggested that during normal conditions extracellular Ca M is kept at an optimal concentration. Finally, conditioned medium was found to contain several CaM-binding proteins. The present findings m ay reflect an earlier unknown function of extracellular CaM in control ling various growth mechanisms in integrated tissues.