THE EFFECT OF LITHIUM ON CHOLINERGICALLY MEDIATED GH RESPONSES IN HEALTHY-VOLUNTEERS

The phosphoinositide (PI) cycle second messenger system mediates the e ffect of muscarinic receptor binding. Inositol, which is an essential substrate for phosphoinositide synthesis penetrates the blood-brain ba rrier 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 cholinergi c overactivity in depression from clinical and experimental observatio ns. Among these, pyridostigmine (PYD) stimulated growth hormone (GH) r elease is found to be elevated relative to healthy controls. PYD/GH re sponses were examined in six healthy male volunteers before and after 10 days of lithium administration. GH responses did not differ signifi cantly after lithium from those observed at baseline. These results su ggest that lithium does not significantly inhibit cholinergically medi ated GH secretion in healthy volunteers and provide further support fo r the selective action of lithium on upregulated cholinergic tracts, c onsistent with uncompetitive inhibition of the phosphoinositide cycle.