Phorbol ester markedly increases the sensitivity of intestinal epithelial cells to 1,25-dihydroxyvitamin D3.
We have used a clonal intestinal epithelial cell line (IEC-18) to study the mechanism of action of 1,25-dihydroxyvitamin D3 (1,25(OH)2D) in vitro. 1,25(OH)2D(10(-7) M) elevated by over 10-fold the mRNA levels for the cytochrome P450 component (P450cc24) of the 1,25(OH)2D-24-hydroxylase. Increased P450cc24 mRNA levels were detectable at 6 h and peaked at 36 h. Below a concentration of 10(-7) M, 1,25(OH)2D had almost no effect. However, addition of phorbol ester for 2 h made the intestine responsive to 1,25(OH)2D concentrations as low as 10(-9) M.
Armbrecht
H J
HJ
Geriatric Research, Education, and Clinical Center, Veterans Affairs Medical Center, St. Louis, MO 63125.
Hodam
T L
TL
Boltz
M A
MA
Chen
M L
ML
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004357:Drug Synergism; D015151:Immunoblotting; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D065668:Vitamin D3 24-Hydroxylase
D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate