Control of urea production, glutamine release and ammonia uptake in the perfused rat liver by the sympathetic innervation.

Abstract

The nervous control of hepatic urea and glutamine release and of ammonia uptake was studied in the rat liver perfused in situ. Electrical stimulation of the nerve bundles around the hepatic artery and the portal vein resulted in a reduction of urea release, of glutamine output and of ammonia uptake. At the same time, as observed before [Hartmann et al. (1982) Eur. J. Biochem. 123, 521-526], nerve stimulation led to a decrease of portal flow as well as to an increase of glucose release and a shift of lactate uptake to output. Noradrenaline infusion mimicked the nerve-dependent metabolic and hemodynamic changes in a first approximation only at the highly unphysiological concentration of 0.1 microM. It was without effect at 0.01 microM, which might be reached in the sinusoids as a result of overflow from the vasculature. In the presence of sodium nitroprusside nerve stimulation no longer reduced urea output, glutamine release and ammonia uptake or portal flow, yet it still increased glucose and lactate release. Phentolamine clearly reduced the alterations after nervous stimulation of urea output, ammonia uptake and portal flow, while propranolol was essentially not effective. The nerve-stimulation-dependent reduction of glutamine release was almost abolished in the presence of phentolamine and lowered to 50% by propranolol. Glucagon stimulated urea output but had no influence on glutamine release, ammonia uptake and portal flow. Nerve stimulation antagonized the glucagon-stimulated urea release. The present results suggest that in the perfused liver alpha-sympathetic hepatic nerves regulate urea release, glutamine output and ammonia uptake predominantly by an indirect mechanism via hemodynamic alterations, but glucose release by a direct mechanism also in the absence of circulatory changes.