PMID- 15322263
OWN - NLM
STAT- MEDLINE
DCOM- 20041103
LR  - 20211203
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 66
IP  - 3
DP  - 2004 Sep
TI  - Diethylstilbestrol is a potent inhibitor of store-operated channels and 
      capacitative Ca(2+) influx.
PG  - 702-7
AB  - We have recently found that diethylstilbestrol (DES), a synthetic estrogen 
      agonist, inhibits thrombin-induced Ca(2+) influx in human platelets, but it 
      remains unclear to what extend this effect might be related to the store-operated 
      Ca(2+) influx pathway. To study the effect of DES on store-operated channels and 
      capacitative Ca(2+) influx, we used rat basophilic leukemia (RBL) cells, vascular 
      smooth muscle cells (SMC), and human platelets, and recorded whole-cell Ca(2+) 
      release-activated Ca(2+) (CRAC) currents and thapsigargin (TG)-induced 
      capacitative Ca(2+) influx. In this study, we demonstrate that extracellular DES 
      produces a dose-dependent and reversible inhibition of CRAC currents in RBL cells 
      (IC(50), approximately 0.5 microM), whereas intracellular DES (25 microM) has no 
      effect. Extracellular DES (up to 30 microM) inhibited only CRAC but did not 
      affect a whole-cell monovalent cation current mediated by TRPM7 channels. DES 
      effectively inhibited TG-induced capacitative Ca(2+) influx in a dose-dependent 
      manner with an IC(50) values of approximately 0.1 microM in RBL cells, <0.1 
      microM in SMC, and approximately 1 microM in human platelets. It is noteworthy 
      that trans-stilbene, a close structural analog of DES that lacks hydroxyl and 
      ethyl groups, had no effect on CRAC current and on store-operated Ca(2+) influx. 
      Thus, we found DES to be a very effective inhibitor of store-operated channels 
      and Ca(2+) influx in a variety of cell types.
FAU - Zakharov, Sergey I
AU  - Zakharov SI
AD  - Boston University School of Medicine, Boston, Massachusetts, USA.
FAU - Smani, Tarik
AU  - Smani T
FAU - Dobrydneva, Yuliya
AU  - Dobrydneva Y
FAU - Monje, Francisco
AU  - Monje F
FAU - Fichandler, Craig
AU  - Fichandler C
FAU - Blackmore, Peter F
AU  - Blackmore PF
FAU - Bolotina, Victoria M
AU  - Bolotina VM
LA  - eng
GR  - HL54150/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels)
RN  - 0 (Cations)
RN  - 0 (Ion Channels)
RN  - 0 (Membrane Proteins)
RN  - 0 (TRPM Cation Channels)
RN  - 731DCA35BT (Diethylstilbestrol)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TRPM7 protein, human)
RN  - EC 2.7.11.1 (Trpm7 protein, rat)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Blood Platelets/drug effects/physiology
MH  - Calcium/*metabolism
MH  - Calcium Channel Blockers/*pharmacology
MH  - Calcium Channels/*metabolism
MH  - Cations/metabolism
MH  - Diethylstilbestrol/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Ion Channels/metabolism
MH  - Membrane Proteins/metabolism
MH  - Myocytes, Smooth Muscle/drug effects/physiology
MH  - Protein Kinases/metabolism
MH  - Protein Serine-Threonine Kinases
MH  - Rabbits
MH  - Rats
MH  - TRPM Cation Channels
EDAT- 2004/08/24 05:00
MHDA- 2004/11/04 09:00
CRDT- 2004/08/24 05:00
PHST- 2004/08/24 05:00 [pubmed]
PHST- 2004/11/04 09:00 [medline]
PHST- 2004/08/24 05:00 [entrez]
AID - 66/3/702 [pii]
AID - 10.1124/mol.66.3. [doi]
PST - ppublish
SO  - Mol Pharmacol. 2004 Sep;66(3):702-7. doi: 10.1124/mol.66.3..