Lithium Inhibition of Adenylate Cyclase Activity: Site of Action and Interaction with Divalent Cations

Abstract

Several studies in man and experimental animals have demonstrated that acute and chronic lithium administration inhibits various stimulated adenylate cyclase activities. Thus lithium inhibits renal antidiuretic hormone (ADH)-stimulated adenylate cyclase activity and thyroid-stimulating hormone (TSH)-stimulated enzyme activity in the thyroid. Other peripheral tissues are also affected by lithium, e.g., platelet and lymphocyte adenylate cyclase. Studies on this enzyme in the central nervous system (CNS) have elucidated that lithium in vitro inhibits the adenylate cyclase in cerebral cortex, corpus striatum, neurohypophysis, hippocampus, pineal gland, and retina. It has been assumed that this inhibition of the adenylate cyclase activity, resulting in dampening of the transmission of neurotransmitter signals, may be of relevance for the mechanism of action of lithium in the treatment of manic-depressive disorders.