Role of Cyclic Nucleotides in the Regulation of Lymphocyte Transformation

Abstract : Studies were conducted to define the roles of cyclic-AMP (cAMP) and cyclic-CMP (cGMP) in lymphocyte mitogenesis. The lymphocyte mitogens staphylococcal enterotoxin B(SEB), concanavalin-A (CON-A), phytohemagglutinin (PHA), and endotoxin, did not stimulate the adenylate cyclase-cAMP system of human or rodent lymphocytes. Similarly, no effect of SEB, CON-A, and PHA on rodent lymphocyte cGMP content was observed during incubations up to 2 hours. Nevertheless, clear-cut and diametrically opposite effects of cAMP and cGMP on lymphocyte DNA synthesis were demonstrated, with cAMP inhibiting and cGMP potentiating this process. These results suggest that the intracellular levels of cAMP and cGMP may be important determinants of lymphocyte growth. However, mitogens do not appear to mediate rapid changes in lymphocytes in cyclic nucleotide content.