The Possible Mediation by Cyclic AMP of the Stimulation of Thymocyte Proliferation by Cyclic GMP 1

Abstract

Summary

Very low (5 × 10^-12 to 10^-10 M), as well as higher (10^-6 to 5 × 10^-6 M) concentrations of cyclic guanosine 3', 5'-monophosphate (cyclic GMP) stimulate the proliferation of rat thymic lymphocytes in vitro, but intermediate concentrations (10^-9 to 10^-7 M) of the cyclic nucleotide do not affect cell proliferation. Other guanosine monophosphates such as guanosine 5'-monophosphate (5'-GMP) and cyclic guanosine 2',3'-monophosphate (cyclic 2',3'-GMP) do not affect thymocyte proliferation.

The maximally mitogenic concentrations (5 × 10^-11 and 5 × 10^-6 M) of cyclic GMP cause rapid (within 10 to 20 min) rises in the cellular cyclic AMP content, but nonmitogenic, intermediate cyclic GMP concentrations do not affect the cellular cyclic AMP content. The higher cyclic GMP levels probably cause the cellular cyclic AMP level to rise by reducing the cyclic AMP-degrading activity of cyclic AMP-phosphodiesterase. The nature of the cyclic AMP-elevating action of the very low cyclic GMP levels is unknown. It is concluded that cyclic GMP can stimulate thymocyte proliferation by two distinct mechanisms both of which are mediated by cyclic AMP.