The synthetic peptide carrying residues 1-40 of chicken alpha(D)-globin, which promotes differentiation in Trypanosoma cruzi epimastigote. stimulated PPtdIns-k, DAG-k, and PA-k activities in a dose-dependent manner. A biphasic behavior only for PPtdlns-k and DAG-k was demonstrated by changes in [P-32]PPtdIns and PtdOH levels, the earlier phase peaking at 3 min with a return to basal levels by 6 min and then a second phase with a sustained increase in time. This behavior was not observed for PA-k: the DGPP levels peaked at 6 min and were sustained in time. PMA pretreatment only abolished the first peak of PPtdIns-k, DAG-k activities. and InsPs/InsP(3) levels. There was also a transient elevation in intracellular calcium concentration, but this variation vas modified only 50% by PMA. The results suggest that peptide 1-40 induces activation of the inositol cycle through lipid kinase activation in a biphasic manner. In this response, the early increase of enzymatic activities would be regulated by PKC and the InsP(3) may only be responsible. in part. for the calcium signaling. (C) 2002 Elsevier Science (USA). All rights reserved.