Continued studies on the isolation and characterization of calmodulin from Giardia lamblia have led to a novel method for the rapid isolation of this protein involving heat denaturation of non-calmodulin proteins and anion exchange chromatography. Characterization of the purified calmodulin show it to be as effective as mammalian calmodulin in activating cAMP phosphodiesterase, and identical in its isoelectric properties. In contrast, the amino acid composition of the parasite calmodulin differed markedly from that of known calmodulins. Studies of the ATPases of G. lamblia showed that the Mg2+-activated enzymes was insensitive to calmodulin antagonists, whereas the Ca2+-dependent enzyme was strongly inhibited. Modulation of the Ca2+-ATPase may be an important physiological function of calmodulin in this parasite. Continued studies on the effects of tricyclic antidepressant drugs on parasitic protozoa disclosed that chlorimipramine suppressed growth of G. lamblia. The mechanism of inhibition has not been elucidated, but does not involve suppression of glucose uptake, as was demonstrated for Leishmania donovani by Zilberstein and Dwyer. Studies on mammalian bioenergetics focused on human platelets. Tricyclic antidepressant drugs partially suppressed the burst of oxygen uptake induced by thrombin. The drugs had no effect on the mitochondrial portion of the burst, but presumably inhibit the oxygenases that catalyze the biosynthesis of prostaglandins. Use of imipramine analogs demonstrated that compounds most effective in inhibiting platelet function were those most effective in blocking bioenergetic phenomena in rat liver and beef heart mitochondria, suggesting a common mechanism of action.
