Alteration of hormone-stimulated cyclic AMP synthesis in guinea pig peritoneal macrophages.

The decrease of PGE-stimulated cyclic AMP synthesis due to pretreatment of intact cells with PGE (hormone-specific desensitization) was shown to be a rapid process in macrophages. Desensitization was found to be extensive after 5-min treatment of macrophages with PGE₂ and almost complete after 20 min. Furthermore, incubation of intact macrophages with colchicine caused a two- to sixfold increase in the rate of PGE₁-stimulated cyclic AMP synthesis in intact macrophages. Colchicine alone did not alter cyclic AMP levels. The enhancing effect of colchicine is related to its ability to disrupt microtubules. Vinblastine, another microtubule-disrupting agent, caused similar enhancement of PGE-stimulated cyclic AMP synthesis; no enhancement was found when lumicolchicine was used. Hormonestimulated cyclic AMP synthesis by colchicine-treated macrophages was also measured after cell homogenization. The enhancement of hormone sensitivity by colchicine was found to be lost upon homogenization. These findings suggest that colchicine acts at the interior of the cell to reversibly affect adenylate cyclase.