The purpose of the present study is to characterize Na+ current activated by growth hormone (GH) releasing hormone (GHRH) and to investigate the effect of somatostatin (SRIF) on that current, since the Na+ current has been suggested to play a pivotal role in the process of GHRH-induced GH secretion. Primary-cultured pituitary somatotrophs were prepared from male Wistar rats. Whole-cell membrane currents were recorded and analyzed by perforated patch clamp system. To isolate Na+ current, K+ and Ca2+ were replaced with Cs+ and Mg2+ respectively in the extracellular solution and cesium aspartate was used for the pipette solution. Furthermore, tetrodotoxin and nifedipine were added to the extracellular solution to eliminate the voltage-gated currents. Under these conditions, GHRH activated a mean inward Na+ current (-1.86±0.33 pA, mean±SE) at potentials between -50 and -20 mV and a smaller current (-0.59±0.13 pA) at potentials between -100 and -80 mV, which were completely blocked by protein kinase A blocker (H-89). In addition, 1~10 nM SRIF partially suppressed these Na+ currents, which were not affected by phosphatase inhibitors (okadaic acid and calyculin A). These results suggest that GHRH activates the Na+ current through phosphorylation by protein kinase A and that SRIF partially suppressed this current and that the current was larger at more positive potentials than at more negative potentials.