Stimulation of Ca2+ efflux by 17β-estradiol is not mediated by soluble guanylyl cyclase. Ca2+ efflux from populations of intact rat hepatocytes was measured at 37 °C using fura-2 pentapotassium salt in the extracellular medium. The traces shown (A and B) are representative of several experiments. 10 nm 17β-estradiol (water-soluble) and 100 μm 8-Br-cGMP were added where indicated by the arrows. Cells were preincubated with either 10 μm NS2028 (A) or no treatment for 5 min, washed 3 times in ice-cold efflux medium (containing NS2028/no treatment), then transferred to a cuvette, and Ca2+ efflux was measured at 37 °C, adding agonist where indicated by the arrows. Calculated mean rates of Ca2+ efflux of at least six experiments from at least three independent hepatocyte preparations are shown in C. *, significantly different from control; **, significantly different from NS2028 alone. SNP, sodium nitroprusside.