Temporal relationship between inositol polyphosphate formation and increases in cytosolic Ca2+ in quiescent 3T3 cells stimulated by platelet-derived growth factor, bombesin and vasopressin.
We determined the temporal relationship between the formation of inositol phosphates and increase in cytosolic [Ca2+] elicited by bombesin, vasopressin and platelet-derived growth factor (PDGF) in quiescent Swiss 3T3 cells. These responses were measured under identical conditions. Bombesin caused a rapid increase in inositol 1,4,5-trisphosphate which coincided with the increase in cytosolic [Ca2+]. This was followed by a slower but marked increase in inositol 1,3,4-trisphosphate and inositol-bisphosphate. Vasopressin elicited a similar sequence of events. In sharp contrast, highly purified porcine PDGF induced increases in cytosolic [Ca2+] and inositol 1,4,5-trisphosphate that were temporally uncoupled: detectable inositol polyphosphate formation occurred after Ca2+ mobilization from intracellular stores. The same temporal dissociation was observed when a recombinant v-sis product was used instead of porcine PDGF. However, PDGF was as effective as bombesin in stimulating the formation of inositol phosphates after 5-10 min of incubation. The data suggest that PDGF increases cytosolic [Ca2+] via a different signal transduction pathway from that utilized by bombesin and vasopressin. These findings have important implications for understanding the signal transduction pathway activated by PDGF.
Nånberg
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Imperial Cancer Research Fund, London, UK.
Rozengurt
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D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007399:Interphase; D007700:Kinetics; D008863:Microspheres; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D013403:Sugar Phosphates / Q000096:biosynthesis*; D014667:Vasopressins / Q000494:pharmacology*
D007295:Inositol Phosphates; D010982:Platelet-Derived Growth Factor; D013403:Sugar Phosphates; D014667:Vasopressins; D001839:Bombesin; D002118:Calcium