Effect of trifluoperazine on DNA synthesis during liver regeneration.

An intraperitoneal injection of the calcium-calmodulin blocker trifluoperazine into rats at 4 hr after a partial hepatectomy produced a strong inhibition of DNA synthesis observed at 24 hr after surgery; but when injection was administered at 20 hr after hepatectomy, it did not produce any effect on DNA replication. These observations indicate that trifluoperazine acted by blocking one or more events involved in triggering DNA replication but it did not affect on-going DNA synthesis. A more detailed study indicated that when trifluoperazine was injected at 4 hr after surgery, a 12 hr delay in the cytosolic calmodulin surge observed between 6 and 12 hr after partial hepatectomy (previous to initiation of DNA replication) and also in the starting of DNA synthesis was produced. These findings suggest that the pre-replicative surge of cytosolic calmodulin could be involved in triggering DNA synthesis observed after partial hepatectomy.