Studies on the cyclic AMP response to prostaglandin in human lymphocytes

It is generally thought that cyclic AMP acts as the second messenger for prostaglandin E in human lymphocytes. We have recently found that the mitogen-induced proliferation of human lymphocytes is no longer inhibited by PGE₂ if the lymphocytes are preincubated overnight prior to the addition of mitogens and PGE₂. In this paper we report that lymphocytes also lose their cyclic AMP response to mitogens after preincubation. The loss of sensitivity to PGE with preincubation can be blocked by cyclohexamide (25 μg/ml). Indomethacin (1 μg/ml) partially blocked the loss of sensitivity, but removal of the glass-adherent cells did not. Since either manipulation effectively stops prostaglandin production in the preincubation cultures, it would appear that indomethacin prevented the loss of sensitivity to PGE₂ by a mechanism other than inhibition of PG synthetase. The addition of phytohemagglutinin to the preincubation cultures also blocked the loss of sensitivity to PGE₂.