Effect of Cyclic Nucleotides, Isoproterenol and Cholera Toxin on DNA Synthesis Triggered by Mitogens

Abstract

The effect of cyclic nucleotides, isoproterenol and cholera toxin on phytohaemagglutinin (PHA), concanavalin A (Con A) and anti-allotype-induced rabbit lymphoid cell proliferation was examined. Cholera toxin in concentrations ranging from 10(-8) microgram to 1 microgram per culture inhibited DNA synthesis, triggered by PHA, Con A and nocardia water-soluble mitogen (NWSM). It had the opposite effect on stimulation with antibodies directed against allotypic specificities of the immunoglobulin light chains: over the entire range of tested concentrations, cholera toxin stimulated DNA synthesis triggered by antibodies to Ab4, Ab5, Ab9 and to Aa1 allotypic specificities. Relatively high concentrations of dibutyryl adenosine 3':5'-cyclic monophosphate (cAMP) and isoproterenol (10(-3) M) inhibited mitogen-stimulated thymidine incorporation; lower concentrations (10(-9) M) had an enhancing effect. A similar enhancing effect was observed when high (10(-3) M) concentrations of dibutyryl guanosine 3':5'-cyclic monophosphate (cGMP) were used.