Pharmacological modification of the Ca2+-pump ATPase activity of human erythrocytes.

The Ca2+-pump ATPase of human RBC membranes appears to be exquisitely sensitive to a variety of amphipathic molecules. The acidic protein calmodulin (CaM) activates the enzyme some three- to fivefold with an apparent Kd of approximately 1-5 nM. A variety of other amphipathic anions, such as acidic phospholipids, free fatty acids, and anionic detergents, are less potent and in some cases less efficacious than CaM, but also activate the enzyme. Similar results have been observed for other CaM-dependent enzymes, and it is suggested that these agents mimic CaM in a general, but rather nonspecific, fashion. Activation of the human RBC Ca2+-pump ATPase by CaM or other amphipathic anions can be selectively antagonized by a wide variety (structurally and pharmacologically) of amphipathic cations. There is no simple relationship between antagonism of CaM in vitro and the general systemic pharmacology of these drugs. The only common feature of such drugs is that they are amphipathic cations. Neutral molecules such as saponin exerted neither CaM-like activity nor CaM antagonism. Great caution is urged in the inferential use of presumed anti-CaM drugs to study biological systems.