The effect of lithium on cholinergically mediated GH responses in healthy volunteers

Abstract

AbstractThe phosphoinositide (PI) cycle second messenger system mediates the effect of muscarinic receptor binding. Inositol, which is an essential substrate for phosphoinositide synthesis penetrates the blood‐brain barrier poorly, and is vulnerable to depletion. Lithium uncompetitively inhibits inositol‐1‐monophosphatase, a key enzyme in the recycling of inositol for the PI messanger system. There is evidence for cholinergic overactivity in depression from clinical and experimental observations. Among these, pyridostigmine (PYD) stimulated growth hormone (GH) release is found to be elevated relative to healthy controls. PYD/GH responses were examined in six healthy male volunteers before and after 10 days of lithium administration. GH responses did not differ significantly after lithium from those observed at baseline. These results suggest that lithium does not significantly inhibit cholinergically mediated GH secretion in healthy volunteers and provide further support for the selective action of lithium on upregulated cholinergic tracts, consistent with uncompetitive inhibition of the phosphoinositide cycle.