Effect of adenosine 3',5'-monophosphate on production of glucose and ammonia by renal cortex.

In studies employing rat renal cortical slices, the addition of adenosine 3',5'-monophosphate (cyclic AMP) to the incubation medium caused an increase in production of glucose from glutamine, glutamate, alpha-ketoglutarate, fumarate, malate, and oxalacetate, but not from glycerol and fructose. These observations suggest that cyclic AMP accelerates a rate-limiting gluconeogenic reaction between oxalacetate and the triose phosphates. The addition to the medium of parathyroid hormone, which is known to increase renal cortical cyclic AMP, also stimulated glucose production from glutamine. When renal cortical slices were incubated in the presence of glutamine, the addition of cyclic AMP caused a fall in tissue glutamate concentration and a rise in ammonia production, as well as an increase in gluconeogenesis. These changes are similar to those observed in renal cortex of rats with induced metabolic acidosis. The present observations are consistent with a previously advanced hypothesis that cortical gluconeogenesis, ammonia production, and glutamate concentration may be interdependent.