Interaction between mitogens upon intracellular Ca2+ pools in murine fibroblasts.
A comparison of the effect of platelet-derived growth factor (PDGF) and bombesin on intracellular Ca2+ 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 Ca2+ concentration ([Ca2+]i) rise, indicating that the two mitogens mobilize Ca2+ 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 [Ca2+]i, whereas pre-treatment with bombesin had only a partial inhibitory effect on the PDGF, Tg and ionomycin [Ca2+]i response, both in the absence and in the presence of external Ca2+. On the other hand, vasopressin and bradykinin, which also stimulate hydrolysis of phosphoinositides in these cells, did not affect the [Ca2+]i response induced by the same agents. These results indicate that, despite the poor production of inositol 1,4,5-trisphosphate (InsP3), PDGF was capable of totally discharging and maintaining discharged the InsP3-sensitive stores of intracellular Ca2+, regardless of whether extracellular Ca2+ was present in the medium. Bombesin only partially caused this effect. On the contrary, bradykinin and vasopressin, after releasing intracellular Ca2+ 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.
Cattaneo
M G
MG
Department of Pharmacology, University of Milan, Italy.
Magrini
L
L
Sparber
S B
SB
Vicentini
L M
LM
D016475:3T3 Cells / Q000187:drug effects*; D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects; D004347:Drug Interactions; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D015759:Ionomycin / Q000494:pharmacology; D051379:Mice; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013268:Stimulation, Chemical; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014667:Vasopressins / Q000494:pharmacology
D015220:Calcium Channels; D010982:Platelet-Derived Growth Factor; D013729:Terpenes; D014667:Vasopressins; D015240:Phorbol 12,13-Dibutyrate; D015759:Ionomycin; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D001839:Bombesin; D001920:Bradykinin; D002118:Calcium