Interaction between mitogens upon intracellular Ca 2+ pools in murine fibroblasts

Abstract

A comparison of the effect of platelet-derived growth factor (PDGF) and bombesin on intracellular Ca 2+ stores was carried out in Swiss 3T3 cells loaded with Fura-2. It was found that the tumor promoter thapsigargin (Tg) almost completely inhibited both the PDGF- and the bombesin-induced intracellular Ca 2+ concentration ([Ca 2+] i) rise, indicating that the two mitogens mobilize Ca 2+ from intracellular pool(s) sensitive to the tumor promoter. It was also found that pre-treatment with PDGF almost totally and persistently (up to at least 30 min) inhibited the bombesin-, Tg- and ionomycin-induced rise in [Ca 2+] i, whereas pre-treatment with bombesin had only a partial inhibitory effect on the PGDF, Tg and ionomycin [Ca 2+] i response, both in the absence and in the presence of external Ca 2+. On the other hand, vasopressin and bradykinin, which also stimulate hydrolysis of phosphoinositides in these cells, did not affect the [Ca 2+] i response induced by the same agents. These results indicate that, despite the poor production of inositol 1,4,5-trisphosphate (InsP 3), PDGF was capable of totally discharging and maintaining discharged the InsP 3-sensitive stores of intracellular Ca 2+, regardless of whether extracellular Ca 2+ was present in the medium. Bombesin only partially caused this effect. On the contrary, bradykinin and vasopressin, after releasing intracellular Ca 2+ allowed an almost total refilling of the pools. It is interesting to note that, at variance with PDGF and bombesin, neither bradykinin nor vasopressin are able to induce a mitogenic response in Swiss 3T3 cells.