Regulation of vasopressin-sensitive adenylate cyclase by calmodulin.

It has recently been demonstrated that an established cell line from pig kidney, LLC-PK1, is a useful model for the study of vasopressin-sensitive adenylate cyclase (Roy, C., and Ausiello, D. A. (1981) J. Biol. Chem. 256, 3415-3422; Roy, C., Hall, D., Karish, M., and Ausiello, D. A. (1981) J. Biol. Chem. 256, 3423-3427). The present study on the regulation of this enzyme has led to the demonstration of the modulation of vasopressin-stimulated adenylate cyclase by Ca2+-calmodulin. The characteristics of calmodulin regulation were similar to those described for other enzymes: (a) activation required micromolar quantities of free Ca2+; (b) maximal enzyme rates were altered but not the Km for hormone activation; (c) activity was inhibitable by trifluoperazine; and (d) activation was dependent on the Mg2+ concentration. These findings should help to define the mechanisms of action of several agents known to alter vasopressin-sensitive adenylate cyclase and cell Ca2+ content.