The aim of this study was to evaluate the participation of serine-threonine kinases and tyrosine kinases (TK) on calcium influx induced by depolarization in the endocrine somatomammotrope cell line GH3. 12.5mM KCl (K+) was used as a depolarization stimulus. H89, a selective PKA inhibitor, significantly reduced Ca²⁺ mobilization induced by depolarization in a concentration-related manner when it was applied before or after K+, and okadaic acid, an inhibitor of Ser/Thr phosphatases which regulates L-type channels stimulated by PKA, increased K+ induced Ca²⁺ entry. When PKC was activated by PMA the peak in [Ca²⁺]_i evoked by K+ as well as the plateau phase were significantly reduced, and Chelerytrine (a PKC inhibitor) potentiated [Ca²⁺]_i rise induced by K+. On the other hand, genistein, a TK inhibitor, reduced the increase in [Ca²⁺]_i evoked by K+, but unexpectedly the tyrosine phosphatase inhibitor ortho-vanadate reduced not only basal calium levels, but calcium influx during plateau phase. Both results suggest different TK may act differentially on VDCC activation. The activation of receptor TKs with EGF or VEGF potentiated Ca²⁺ influx induced by K+, and AG1478 (an EGFR inhibitor) decreased it. But, the inhibition of the non receptor TK, pp60 c-Src, enhanced Ca²⁺ influx induced by K+. The present study strongly demonstrates that kinases and phosphatases regulate VDCC activity in the pituitary cell line GH3: PKA and RTKs, such as VEGFR and EGFR, enhance calcium influx induced by depolarization, while PKC and c-Src have an inhibitory effect.