The intracellular calcium antagonist, TMB-8, inhibits prolactin gene expression in GH3 cells.
We examined the effects of the drug, TMB-8, which promotes sequestration of intracellular Ca2+, on the ability of extracellular Ca2+ to stimulate prolactin gene expression in GH3 cells. TMB-8 inhibited prolactin mRNA levels in a dose-dependent manner in the concentration range of 2.5-10 microM. Prolactin mRNA levels were increased about 18-fold by the addition of 0.1 mM CaCl2, and about 25-fold by the addition of 0.4 mM CaCl2. Addition of 10 microM TMB-8 reduced these levels to about 4-fold and 7-fold, respectively. At 10 microM TMB-8 did not effect total protein synthesis or the Ca2+-induced aggregation of the cells, indicating a selective inhibition by the drug of prolactin gene expression. Both TMB-8 and the calmodulin inhibitor, calmidazolium, reversed the effects of Ca2+ on prolactin mRNA levels in cells that had been pretreated for 2 days with 0.4 mM CaCl2.
Preston
G M
GM
Department of Anatomy, University of Connecticut Health Center, Farmington 06032.
White
B A
BA
D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D002460:Cell Line; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D010673:Pheochromocytoma / Q000235:genetics / Q000378:metabolism; D011388:Prolactin / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism
D007093:Imidazoles; D012333:RNA, Messenger; C031938:calmidazolium; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D011388:Prolactin; D002122:Calcium Chloride; D002118:Calcium