Neurotransmitters, hormones, and cyclic nucleotides in lymphocyte regulation

Lymphocytes bear receptors for a wide variety of neurotransmitters, hormones, and other mediators that influence cellular functions in part through alterations in cyclic nucleotide metabolism. A sizable list of agents that increase cyclic AMP levels now includes adenosine (Ra), epinephrine (beta), glucocorticosteroids, histamine (H2), prostaglandins (A, E), and bacterial products (lipopolysaccharide, cholera toxin). We have found no evidence for lymphocyte cyclic AMP responses to adenosine Ri agonists or to enkephalins. Present data suggest a role for cyclic AMP in promoting the differentiation of immature lymphocytes, whereas elevated cyclic AMP levels are associated with inhibition of mature, differentiated lymphocyte functions. Opposing these effects of cyclic AMP are those of cyclic GMP and an expanding collection of compounds that increase its levels: acetylcholine (muscarinic), ascorbate, calcium ionophore, hydroperoxides of arachidonic acid, hypoxanthine derivatives, interleukin 1, serotonin, thymic hormones, and plant lectin mitogens. The biochemical pathways mediating cyclic GMP increases and mechanisms by which cyclic GMP may enhance immunological responses are being intensively studied.