Gly-His-Lys, a tripeptide isolated from human plasma that increases the growth rate of many cells, stimulated in dose-dependent fashion the activity of phosphorylase a in isolated rat hepatocytes. Such effect was associated to increases in both IP3 production and [Ca++]i. Interestingly, these effects of Gly-His-Lys were antagonized by losartan, a nonpeptide angiotensin II receptor antagonist (AT1 selective), which suggested that these receptors were involved in its effect. Binding competition experiments using the radioligand [125I][Sar1-Ile8]angiotensin II clearly indicated that Gly-His-Lys interacts with AT1 receptors. It was also observed that other histidine-containing tripeptides were also capable of interacting with these receptors.