Increase of Cyclic Adenosine 3′:5′-Monophosphate Concentration in Transplantable Lymphoma Cells by Vinca Alkaloids

In an attempt to study the effects of several substances on intracellular cyclic adenosine 3′:5′-monophosphate (cAMP) concentration in tumor cells, lymphoma cells were incubated with biogenic amines (histamine, norepinephrine, epinephrine, and isoproterenol), prostaglandin E1 (PGE1), and Vinca alkaloids (vincristine and vinblastine). All substances tested increased intracellular cAMP in the presence of theophylline. Combined administration of Vinca alkaloid with biogenic amines or PGE1 produced an additive increase of cAMP in lymphoma cells. Vinca alkaloids depressed cAMP phosphodiesterase activity, but this depression was too weak to explain an increase of cAMP. In lymphoma cell homogenate, biogenic amines and PGE1 increased cAMP but Vinca alkaloids failed to do so, suggesting destruction of the receptor and/or transducer mechanism for Vinca alkaloids by homogenization. The effect of biogenic amines, PGE1, and Vinca alkaloids on cAMP was depressed by pretreatment of lymphoma cells with phospholipases C and A2. In vivo treatment of lymphoma cells with vinblastine gradually reduced the receptor and/or transducer mechanism for Vinca alkaloids, PGE1, and isoproterenol. It is suggested that Vinca alkaloids elevated cAMP concentration in lymphoma cells by acting on the plasma membrane. The receptor for Vinca alkaloids is distinct from those for biogenic amines and PGE1.