CYCLIC-AMP PHOSPHODIESTERASES IN HUMAN-LYMPHOCYTES

The function of lymphocytes, like platelets, has been shown to be inhi bited by agents which increase intracellular cyclic AMP. Two high-affi nity cAMP phosphodiesterases (PDEs), the cyclic GMP-inhibited cAMP pho sphodiesterase, PDE3, and the cAMP-specific phosphodiesterase PDE4, ar e known to regulate cAMP concentration in haemopoietic cells by degrad ing cAMP to AMP. We characterized the relative contribution of the two PDEs to total lymphocyte PDE activity We then determined which of the different gene products, PDE3A, typical of myocardium and platelets, or PDE3B, typical of adipocytes, were present in lymphocytes. The PDE3 -specific inhibitor, milrinone, and the PDE4 inhibitor, rolipram, supp ressed hydrolysis by 70% and 30% respectively, which indicated that bo th PDE4 and PDE3 were present, and that PDE3 was predominant. RT-PCR y ields the expected size fragment for the primer pair PDE3B and not for PDE3A. The DNA sequence obtained had >95% identity with PDE3B. PDE3B appears to be the major cAMP PDE in lymphocytes. In contrast to human platelets, human lymphocytes appear to contain the PDE3B subtype. Sinc e PDE3B in adipocytes is subject to hormonal regulation, lymphocytes m ay be similarly modulated, Understanding the role of cAMP regulation a nd the involvement of cAMP in lymphocyte function may have important i mplications in drug development.