Diethylstilbestrol increases intracellular calcium in lens epithelial cells.
The effects of diethylstilbestrol (DES) on steady-state intracellular calcium concentration ([Ca(2+)](i)) and resting Ca(2+) influx were examined in primary cultures of bovine lens epithelial cells using conventional fluorometric techniques (Fura-2). At low concentrations (10 microM), DES usually induced relatively rapid increases in [Ca(2+)](i) that occurred over an interval of 10-50 s and that persisted for several minutes in the continued presence of the drug. In about 10% of the cells, cyclic oscillations in [Ca(2+)](i) were seen after adding 10 microM DES. At higher concentrations (100 microM), the drug induced more prolonged increases in [Ca(2+)](i) lasting several minutes. DES did not affect Mn(2+) quench determinations of resting Ca(2+) influx, and neither 100 microM GdCl(3), which blocked resting Ca(2+) influx, nor low [Ca(2+)](o) solutions substantially diminished the influence of DES on [Ca(2+)](i). Pretreatment of cells with the smooth endoplasmic reticulum Ca(2+) ATPase (SERCA) inhibitors cyclopiazonic acid (CPA) or thapsigargin completely abolished the effect of 10 microM DES on [Ca(2+)](i), while the IP(3) receptor blocker 2-aminoethoxydiphenyl borane (2-APB) had no effect. These results indicate that DES releases CPA-sensitive stores of intracellular Ca(2+), perhaps by inhibiting SERCA-dependent Ca(2+) sequestration.
Samadi
Abbas
A
Department of Biochemistry, College of Osteopathic Medicine, Kirksville, MO 63501, USA.
Cenedella
Richard J
RJ
Carlson
C George
CG
D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002417:Cattle; D004054:Diethylstilbestrol / Q000494:pharmacology*; D018871:Endoplasmic Reticulum, Smooth / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D016257:Fura-2 / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007908:Lens, Crystalline / Q000166:cytology; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019284:Thapsigargin / Q000494:pharmacology
D001896:Boron Compounds; D015220:Calcium Channels; D007211:Indoles; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D019284:Thapsigargin; D004054:Diethylstilbestrol; D005682:Gadolinium; C109986:2-aminoethoxydiphenyl borate; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; C038958:gadolinium chloride; D002118:Calcium; D016257:Fura-2; C000543:cyclopiazonic acid