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

Abstract

1. The nervous control of hepatic urea and glutamine release and of ammonia uptake was studied in the rat liver perfused in situ.2. 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 Eur. J. Biochem. 123, 521 -5261, 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.3. Noradrenaline infusion mimicked the nerve-dependent metabolic and hemodynamic changes in a first approximation only at the highly unphysiological concentration of 0.1 pM. It was without effect at 0.01 pM, which might be reached in the sinusoids as a result of overflow from the vasculature.4. 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.5. 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.6. Glucagon stimulated urea output but had no influence on glutamine release, ammonia uptake and portal flow. Nerve stimulation antagonized the glucagon-stimulated urea release.7. The present results suggest that in the perfused liver wsympathetic 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.The liver is innervated by sympathetic and parasympathetic nerves [l-31. It was shown previously that in the isolated perfused rat liver electrical stimulation of the nerve bundles around the hepatic artery and the portal vein resulted in an increase of glucose output, a switch from lactate uptake to output and a decrease of portal flow [4] combined with a change of the intrahepatic microcirculation [5, 61, a reduction of oxygen uptake [5,7] and an overflow of noradrenaline into the hepatic vein [8]. All nerve actions were predominantly aadrenergic. It was observed recently that hepatic nerve stimulation decreased ketogenesis [9]. Possible effects of nerve stimulation on hepatic 'nitrogen' metabolism have not been studied so far either in vivo or in the isolated perfused organ. Therefore it was the object of the present investigation to clarify whether the hepatic nerves can also regulate urea, glutamine and ammonia metabolism besides glucose and lactate exchange. A preliminary report on some of the findings has appeared previously [lo].

Increase of urate formation by stimulation of sympathetic hepatic nerves, circulating noradrenaline and glucagon in the perfused rat liver

“…Piischel, Institut ffir Biochemie, Georg-August-Universitfit, Humboldtallee 23, D-3400 G6ttingen, FRG hepatic vein [6,14], a transient release of Ca 2+ followed by reuptake [13] and, conversely, a transient uptake of K ÷ followed by release [13]. All changes could partly be mimicked by circulating noradrenaline [5,[8][9][10] or phenylephrine [11,13], yet only at hyperphysiological concentrations. They were mediated predominantly via orsympathetic receptors.…”

“…An unspecific interference with urate formation could therefore be excluded. Thus, in rat liver all nerve stimulation-dependent metabolic and hemodynamic changes so far observed [5,6,9,10] appear to be mediated predominantly by areceptors.…”

“…The flow reduction was accompanied by a redistribution of the hepatic microcirculation [7,8]. Glucose and lactate • output increased [5,6], and ketone body formation [9], urea and glutamine production as well as ammonia uptake [10] and oxygen consumption decreased [7,8,11]; furthermore para-nitrophenol conjugation decreased [12] and glutathione efflux increased [13]. Stimulation of the nerve bundles also caused an overflow of noradrenaline into the Correspondence address: G.P.…”

Grain Proteins Digested by Trypsin Modify Plasma Amino Acid Concentration in Chickens

“…), protein turnover (i.e. protein synthesis, Ito (Ballé and Jungermann, 1986;Mortimore et al, 1988;Gardemann et al, 1992). In the present study, to minimize the influence of hepatic metabolism of nutrients, blood samples were derived from mesenteric vein to directly determine the change in plasma nutrient concentrations after oral administration of nutrients.…”

Modulation by somatostatin of nerve‐mediated activation of glycogenolysis in the perfused rat liver

“…In the in situ perfused rat liver electrical stimulation of the hepatic nerves around the hepatic artery and portal vein was shown to increase glucose and lactate output [5] as Enzymes: Glucose dehydrogenase (EC 1.1.1.47); glutamatepyruvic transaminase (EC 2.6.1.2); lactate dehydrogenase (EC 1.1. 1.27) well as urate and allantoin formation [6] and to reduce ketogenesis [7], urea release and ammonia uptake [8] as well as oxygen consumption [9,10]. The nerve action could be blocked by the ablocking agent phentolamine and therefore, it was predominantly mediated by or-receptors [5].…”