Lithium but not cholinergic ligands influence guanylate cyclase activity in intact human lymphocytes

Abstract

The presence of guanylate cyclase in intact circulating human lymphocytes and the sensitivity of this enzyme to stimulation by sodium nitroprusside could be confirmed. However, in contrast to other observations all attempts failed to stimulate the enzyme by cholinergic agonists, despite the use of M1 as well as M2 selective agonists. These findings do not support the assumption that cholinergic recognition sites on human lymphocytes described by many groups are part of a functioning muscarinic transducing mechanism. While several other neuroreceptor agonists were also unable to affect lymphocyte guanylate cyclase activity, lithium was found to potently inhibit the stimulation of guanylate cyclase by sodium nitroprusside at an intracellular concentration close to the therapeutic plasma levels. It is suggested that the effects of lithium on guanylate cyclase activity in human lymphocytes could be related to a possible mechanism of action of lithium in affective disorders.