TY - JOUR
T1 - The pure anti-oestrogen ICI 182,780 (Faslodex™) activates large conductance Ca 2+-activated K + channels in smooth muscle
AU - Dick, Gregory M.
PY - 2002
Y1 - 2002
N2 - Oestrogen and tamoxifen activate large conductance Ca 2+-activated K + (BK Ca) channels in smooth muscle through a non-genomic mechanism that depends on the regulatory β1 subunit and an extracellular binding site. It is unknown whether a 'pure' anti-oestrogen such as ICI 182,780 (Faslodex™), that has no known oestrogenic properties, would have any effect on BK Ca channels. Using single channel patch clamp techniques on canine colonic myocytes, the hypothesis that ICI 182,780 would activate BK Ca channels was tested. ICI 182,780 increased the open probability of BK Ca channels in inside-out patches with an EC 50 of 1 μM. These data suggest that molecules with the ability to bind nuclear oestrogen receptors, regardless of oestrogenic or anti-oestrogenic nature, activate BK Ca channels through this nongenomic, membrane-delimited mechanism. The identity and characteristics of this putative binding site remain unclear; however, it has pharmacological similarity to oestrogen receptors α and β, as ICI 182,780 interacts with it.
AB - Oestrogen and tamoxifen activate large conductance Ca 2+-activated K + (BK Ca) channels in smooth muscle through a non-genomic mechanism that depends on the regulatory β1 subunit and an extracellular binding site. It is unknown whether a 'pure' anti-oestrogen such as ICI 182,780 (Faslodex™), that has no known oestrogenic properties, would have any effect on BK Ca channels. Using single channel patch clamp techniques on canine colonic myocytes, the hypothesis that ICI 182,780 would activate BK Ca channels was tested. ICI 182,780 increased the open probability of BK Ca channels in inside-out patches with an EC 50 of 1 μM. These data suggest that molecules with the ability to bind nuclear oestrogen receptors, regardless of oestrogenic or anti-oestrogenic nature, activate BK Ca channels through this nongenomic, membrane-delimited mechanism. The identity and characteristics of this putative binding site remain unclear; however, it has pharmacological similarity to oestrogen receptors α and β, as ICI 182,780 interacts with it.
KW - 17-β Oestradiol
KW - MaxiK channel
KW - Slo
KW - Tamoxifen
KW - β1 subunit
UR - http://www.scopus.com/inward/record.url?scp=0036024230&partnerID=8YFLogxK
U2 - 10.1038/sj.bjp.0704807
DO - 10.1038/sj.bjp.0704807
M3 - Article
C2 - 12145095
AN - SCOPUS:0036024230
SN - 0007-1188
VL - 136
SP - 961
EP - 964
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 7
ER -