A) ET-1 (50 nM) was given for various times to mIMCD-3 and phosphorylation of ERK1/2 measured by Western blot. Peak phosphorylation occurred after 15 min of ET-1 exposure. B) ETA receptor antagonism (BQ123) lead to an increase in 15 min ET-1 stimulated ERK1/2 phosphorylation. C) ETB receptor antagonism (BQ788) lead to a decrease in 15 min ET-1 dependent ERK1/2 phosphorylation. D) The MEK1 inhibitor, PD98,059, prevented the phosphorylation of ERK1/2; however, PD98,059 did not prevent the ET-1 dependent increase in mIMCD-3 nitrite 15 production (E) (Two-Factor ANOVA: Drug p = 0.46, ET-1 treatment p < 0.0002, interaction p = 0.91). Note nitrite production was calculated as pmol nitrite/ mg protein/ h. * P<0.05 compared to time 0 or vehicle. N = 4.