Studies to elucidate the function of calmodulin (CaM) in Giardia lamblia focused on calcium transport by the intact trophozoites and ATPase activity. CA2+ uptake by the parasite was both rapid and substantial: 224 + 73 nmoles Ca2+/mg protein/min. The uptake is an active process and appears to be mediated by a membrane-bound Ca2+ activated ATPase. Both the Ca2+ uptake and the particulate ATPase were inhibited by micromolar concentrations of the CaM antagonists fluphenazine and trifluoperazine. Studies of the effects of tricyclic antidepressant drugs on the in vitro growth of Trypanosoma cruzi showed that chlorimipramine and 2-nitrodesmethylimipramine were cidal to the epimastigotes in micromolar concentations. Differences in susceptibility and development of drug resistance were evident in various T. cruzi stocks. Continued work on the novel Mn2+ activated NADPH dehydrogenase provided new evidence that this enzyme may be a specific biochemical marker for the Entamoeba. A survey of the respiratory metabolism of Entamoeba invadens disclosed that this pathogenic parasite has similar properties of electron transport, sensitivity to inhibitors, and respiratory rate as trophozoites of E. histolytica. Mammalian studies were concluded on the effects of tricyclic antidepressant drugs on energy metabolism of human platelets. Cogeners of imipramine that were most effective in suppressing metabolism of platelets were similarly effective in other biological systems (liver and heart mitochondria, chromaffin granules) suggesting a common mode of action, presumably at the membrane locus.
