Possible Involvement of Calmodulin in the Induction of Phosphodiesterase by Cyclic Adenosine 3', 5'-Monophosphate in Dictyostelium discoideum

We reported previously that Ca2+ participates in the induction of phosphodiesterase [EC 3.1.4.17] (PDE) by cyclic adenosine 3', 5'-monophosphate in Dictyostelium discoideum [F. Yamasaki and H. Hayashi, J. Biochem. (Tokyo), 92, 1911 (1982)]. The results reported here raise the possibility that the action of Ca2+ in the induction of PDE may be mediated by calmodulin. Cells were incubated with cyclic adenosine 3', 5'-monophosphate in the presence of various calmodulin inhibitors, and the cellular and extracellular PDE activities were determined. All calmodulin inhibitors reduced the inductions of both cellular and extracellular PDEs, and the order of effectiveness was trifluoperazine, chlorpromazine, dibucaine, tetracaine and W-7. It was confirmed that these calmodulin inhibitors neither decrease the cell viability, nor reduce PDE activity directly. The inhibition of PDE induction by dibucaine was not overcome by addition of phospholipid and CaCl2, ruling out the participation of Ca2+ in membrane phospholipid. We also ruled out any involvement of Ca2+-activated phospholipid-dependent protein kinase, which is reported to be inhibited by calmodulin inhibitors, because this activity was not found in the slime mold even in the absence of the inhibitors. On the basis of the above results, calmodulin may be considered to play an important role in the induction of PDE by cAMP in the slime mold