Role of Ca2+ in t-PA production by human embryonic lung diploid fibroblast, IMR-90 cells, stimulated by proteose peptone.
Proteose peptone (p.peptone) remarkably induced tissue plasminogen activator (t-PA) activity in the conditioned medium of confluently cultured human embryonic lung diploid fibroblast, IMR-90 cells, in a dose-dependent manner. t-PA activity correlated well with the amount of t-PA antigen found in the conditioned medium of IMR-90 cells stimulated by p.peptone. t-PA production by IMR-90 cells stimulated by p.peptone was dependent on extracellular Ca2+ concentration and maximum t-PA production required approximately 3.6 mM extracellular Ca2+. Conversely, elimination of Ca2+ from the culture medium by EGTA, Ca2+ chelate agent, strongly inhibited t-PA production induced by p.peptone. t-PA production induced by p.peptone was inhibited in a dose-dependent manner by Verapamil, which inhibits Ca2+ uptake through the slow channels and also by W-7, an inhibitor of calmodulin. These results suggested that influx of extracellular Ca2+ into IMR-90 cells was caused by p.peptone and induced t-PA production by the cells.
Suzuki
A
A
Research Institute of Life Science, Snow Brand Milk Products Co. Ltd, Tochigi, Japan.
Itagaki
Y
Y
Shima
N
N
Mitsuda
S
S
Higashio
K
K
Kawanishi
G
G
D001667:Binding, Competitive; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002364:Caseins / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology*; D010461:Peptones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000096:biosynthesis*; D014700:Verapamil / Q000494:pharmacology
D002364:Caseins; D010446:Peptide Fragments; D010461:Peptones; D013449:Sulfonamides; C018135:proteose-peptone; D003609:Dactinomycin; D000001:Calcimycin; D004533:Egtazic Acid; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; C017967:W 7; D003513:Cycloheximide; D014700:Verapamil; D010959:Tissue Plasminogen Activator; D002118:Calcium