title: Mechanisms through which PDGF alters intracellular calcium levels in U-1242 MG human glioma cells.
abstract: PDGF-BB induces a rapid, sustained increase in intracellular calcium levels in U-1242 MG cells. We used several calcium channel blockers to identify the types of channels involved. L channel blockers (verapamil, nimodipine, nicardipine, nitrendipine and taicatoxin) had no effect on PDGF-BB induced alterations in intracellular calcium. Blockers of P, Q and N channels (omega-agatoxin-IVA, omega-conotoxin MVIIC and omega-conotoxin GVIA) also had no effect. This indicates that these channels play an insignificant role in supplying the Ca2+ necessary for PDGF stimulated events in U-1242 MG cells. However, a T channel blocker (NDGA) and the non-specific (NS) calcium channel blockers (FFA and SK&F 9365) abolished PDGF-induced increases in intracellular calcium. This indicates that PDGF causes calcium influx through both non-specific cationic channels and T channels. To study the participation of intracellular calcium stores in this process, we used thapsigargin, caffeine and ryanodine, all of which cause depletion of intracellular calcium stores. The PDGF effect was abolished using both thapsigargin and caffeine but not ryanodine. Collectively, these data indicate that in these human glioma cells PDGF-BB induces release of intracellular calcium from caffeine- and thapsigargin-sensitive calcium stores which in turn lead to further calcium influx through both NS and T channels.
authors.affiliation: Department of Pathology, The Ohio State University, Columbus 43210, USA.
authors.forename: H E
authors.initials: HE
authors.lastname: Saqr
authors.forename: Z
authors.initials: Z
authors.lastname: Guan
authors.forename: A J
authors.initials: AJ
authors.lastname: Yates
authors.forename: B T
authors.initials: BT
authors.lastname: Stokes
mesh_terms: D000077214:Becaplermin; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000145:classification / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004546:Elapid Venoms / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005439:Flufenamic Acid / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D009637:Masoprocol / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism; D009529:Nicardipine / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D012433:Ryanodine / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology; D020960:omega-Conotoxins
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004546:Elapid Venoms; D004791:Enzyme Inhibitors; D007093:Imidazoles; D009363:Neoplasm Proteins; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; C079205:taicatoxin; C075851:omega-conotoxin-MVIIC; D012433:Ryanodine; D000077214:Becaplermin; D002110:Caffeine; D009553:Nimodipine; D005439:Flufenamic Acid; D019284:Thapsigargin; D009637:Masoprocol; D020866:omega-Conotoxin GVIA; D009568:Nitrendipine; D014700:Verapamil; D009529:Nicardipine; D000252:Calcium-Transporting ATPases; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium