Effect of lithium on glucagon-stimulated cyclic AMP excretion in rats.

Abstract

Rats were given food containing lithium in amounts leading to serum lithium concentrations of 0.6‐1.1 mM, and the urinary excretion of cyclic AMP after subcutaneous injection of glucagon was determined. The unstimulated cyclic AMP excretion was the same in the lithium‐treated and in the control rats, but after glucagon administration the lithium‐treated rats excreted significantly higher amounts of cyclic AMP than the control rats. This occurred whether lithium had been given during two days or six weeks before the glucagon injection. At all dose levels of glucagon, within the range of 50‐1000 μg/kg b. wt., the response of the lithium‐treated rats was about 70% higher than in the control rats. The increased cyclic AMP excretion was not due to the lithium‐induced polyuria since the difference between the lithium‐treated rats and control rats was also present when polyuric lithium rats were compared with polyuric control rats. The higher excretion of cyclic AMP could not be accounted for by an increased activity of the adenyl cyclase or a decreased degradation rate of cyclic AMP measured in liver homogenates. A somewhat lowered binding capacity of the protein kinases for cyclic AMP was found in the lithium‐treated rats; this might cause or contribute to the increased urinary cyclic AMP excretion.