Role of Ca2+ in serum-stimulated Na+ influx in normal and transformed cells.
Previous studies in human foreskin fibroblasts suggested that the mechanism by which serum stimulates Na+ influx is via a Ca2+-calmodulin-mediated event. In the present experiments in normal WI-38 cells (human lung fibroblasts), both the intracellular Ca2+ antagonist 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8) and the potent calmodulin antagonist trifluoperazine (TFP) blocked serum-stimulated Na+ influx [TMB-8 concentration causing half-maximal inhibition (Ki) = 15 microM and TFP Ki = 10 microM]. Similar results were obtained in Swiss 3T3 cells. In contrast, in transformed WI-38 or Swiss 3T3 cells neither TMB-8 nor TFP had any effect on serum-stimulated Na+ influx (TMB-8 Ki greater than 100 microM and TFP Ki greater than 100 microM). In addition, when 45Ca2+ efflux measurements were made on normal and transformed cells, serum stimulated significant 45Ca2+ efflux (P less than 0.05) from WI-38 and Swiss 3T3 cells, while having no effect on 45Ca2+ efflux from simian virus 40 (SV40)-WI-38 or SV40-Swiss 3T3 cells. However, an elevation of intracellular Ca2+ can stimulate Na+ influx, since it was found that A23187 mimicked the effects of serum in both normal and transformed cells. These results suggest that the Ca2+-calmodulin-mediated event, which is thought to be involved in serum-stimulated Na+ influx in normal cells, may be bypassed or overridden in transformed cells.
Owen
N E
NE
Villereal
M L
ML
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001769:Blood; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002132:Calcium Radioisotopes; D002147:Calmodulin / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D002472:Cell Transformation, Viral; D003470:Culture Media; D005347:Fibroblasts; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008168:Lung / Q000166:cytology; D012964:Sodium / Q000378:metabolism*; D014268:Trifluoperazine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D002147:Calmodulin; D003470:Culture Media; D007473:Ion Channels; D014268:Trifluoperazine; D000001:Calcimycin; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D000584:Amiloride; D012964:Sodium; D002118:Calcium