TI - Rapid effects of ICI182 , 780 and 17alpha-estradiol on ERK1/2 activation . AB - To characterize the pharmacologic properties of ERK activation , we used mERhigh cells to study the effectiveness of the potent antiestrogen ICI182,780 ( 1 mumol/l ) and the inactive E2 stereoisomer 17alpha-estradiol ( 10 nmol/l ) . We used concentrations of these compounds shown by others to be effective in inhibiting the transcriptional activity of E2 . We had also previously shown that a 10 nmol/l 17alpha-estradiol concentration could elicit another type of nongenomic estrogenic effect in our GH3/B6/F10 pituitary tumor cell model - rapid prolactin release [15] . ICI182,780 alone induced an activation pattern very similar to that seen with E2 but with an earlier first peak ( Fig 11a ) . A 30 min ICI182,780 preincubation before a subsequent 1 pmol/l E2 challenge did not significantly change the E2 activation pattern , although the first peak again appeared at 6 min ( the ICI182,780 pattern ) and there was a more pronounced inactivation at 10 and 20 min ( compare Fig 11b with Figs 7a and 11a ) . However , simultaneous application of ICI182,780 ( 1 mumol/l ) and E2 ( 1 pmol/l ) blunted the response and altered the kinetics of ERK PHOSphorylation , shifting the now single weak activation to later times ( 20-60 min ; Fig 11c ) . The E2 stereoisomer ( 17alpha-estradiol ) provoked a slightly delayed and blunted response also , but with some other interesting features ( Fig 11d ) . A significant dephosphorylaTION occurred before the major activation peak , a return to baseline PHOSphorylation levels followed the 20 min activation peak , and no second activation peak occurred at 60 min .