Nervous control of liver metabolism and hemodynamics.

Abstract

Besides being a center of intermediary metabolism, a center of defense and a control center for the hormonal system, the liver acts as the glucose reservoir of the organism and, moreover, as an important blood reservoir, by taking up or releasing glucose and blood. The many diverse hepatic functions are controlled by the substrate concentrations in blood, the cirulating hormone levels, the biomatrix and the autonomic hepatic nerves. In this review, the present knowledge of the metabolic and hemodynamic effects, the mechanism of action and the function of the hepatic nerves, as studied in the isolated perfused liver, are summarized.Effects of heptic nerve stimulationIn perfused rat liver, activation of the sympathetic liver nerves increases glucose and lactate release, urate and allantoin formtiuon, decreases ketogenesis, urea release, ammonia uptake, xenobiotics conjugation, bile flow and bile acid secretion as well as oxygen utilization, and causes an overflow of noradrenaline into the hepatic vein. Furthermore, sympathetic stimulation decreases the flow and elicits an intrahepatic redistrubution as well as a mobilization of blood by the closing of sinusoids. Activation of parasympathetic nerves enchances glucose utilization and causes re‐opening of previously closed sinusoids. The actions of hepatic nerves are modulated by the hormones glucagon, insulin, adrenaline, noradrenaline, vasopressin and angiotensin.Extrahepatocellular signal chain of sympathetic nerve stimulationThe release of noradrenaline from the nerve endings and all effects of electrical nerve stimulation are strictly dependent on the presence of extracellular calcium. Sympathetic nerves regulate the hepatic metabolism of carbohydrates and ketone bodies and the conjugation of xenobiotics directly via interaction with non‐parenchymal and parenchymal liver cells. However, sympathetic nerves regulate metabolism of nitrogenous compounds indirectly via reduction of blood flow. Studies with adrenergic and prostanoid agonists and antagonists support the following mechanism. Noradrenaline, released from the nerve endings via α1‐adrenergic receptors, directly interacts with periportal hepatocytes and also stimulates prostanoid formation in nearby non‐parenchymal liver cells. Prostanoids, in turn, modulate metabolism in parenchymal cells. About 50% of the metabolic nerve effects in rat liver are mediated via signal propagation through gap junctions. By this mechanism, rat liver apparently compensates the scarce innervation of only a few parenchymal and non‐parenchymal cells in the proximal periportal zone.Intrahepatocellular signal chain of sympathetic nerve stimulationSympathetic nerve stimulation of the perfused rat liver causes an increase in the activity of glycogen phosphorylase and a decrease in the activity of glycogen synthase, but leaves the activity of pyruvate kinase unaltered; fructose 2,6‐bisphosphate and cAMP are only slightly enhanced. Various studies strongly support the notion that the intracellular signal chain is propagated by production of inositol 1,4,5‐triphosphate and an increase in cytosolic calcium.In conclusion, hepatic nerves, together with the hormonal system, are directly involved in the regulation of liver metabolism and hemodynamics.