DIFFERENCES IN THE FORSKOLIN ACTIVATION OF ADENYLATE CYCLASES IN WILD-TYPE AND VARIANT LYMPHOMA-CELLS

Abstract

The ability of the diterpene forskolin to stimulate cAMP accumulation in intact cell and membrane preparations of wild-type S49 lymphoma cells [mouse] (WT) and a number of variants was confirmed. A number of salient new findings have emerged. A time delay in forskolin stimulation of cAMP accumulation and adenylate cyclase (t1/2 [half-life] .simeq. 1.5 min) occurred in all hormone-sensitive WT and variant cell and membrane preparations tested. The time delay was missing in the adenylate cyclase-deficient variant (cyc-) of the S49 lymphoma cell, which also lacks functional adenylate cyclase-coupling proteins. The simultaneous addition of epinephrine and forskolin to WT cells or to membrane preparations eliminated the time delay. Forskolin stimulation of intact WT cells did not appear to desensitize adenylate cyclase. The activation of WT adenylate cyclase by forskolin was biphasic with respect to concentration, with both high- and low-affinity components being apparent. In cyc-, only the low-affinity component was detected.