Further studies on the mechanism of phosphorylase activation in rabbit liver in response to splanchnic nerve stimulation

Abstract

SUMMARY1. The mechanism of activation of liver phosphorylase after splanchnic nerve stimulation has been investigated in rabbits and compared with the effects of intraportal injections of noradrenaline.2. The increase in the activity of liver phosphorylase-a, the active form of this key glycogenolytic enzyme, in response to injections of noradrenaline was blocked by ,f-adrenergic antagonists, but not by a-adrenergic antagonists, suggesting that the effect of noradrenaline is mediated mainly through f-adrenoceptors in vivo. In contrast, the increase in phosphorylase activity in response to stimulation of the peripheral end of the splanchnic nerve was resistant to both a-and f-adrenoceptor blockade.3. When diltiazem and verapamil, selective Ca2+ antagonists that restrict calcium influx across the cell membrane, were infused intraportally, the phosphorylase response to splanchnic nerve stimulation was virtually abolished, while the response to noradrenaline was unaltered.4. Infusion of the prostaglandin-synthesis inhibitor indomethacin at a dose of 3-4 ,sg/min was found to block the activation of liver phosphorylase in response to stimulation of the splanchnic innervation. 5. These results suggest that the mechanism whereby stimulation ofthe sympathetic innervation to the liver leads to activation of phosphorylase is not mediated by either a-or 8f-adrenoceptors, but appears to depend upon prostaglandin formation and influx of Ca2+ ions into the hepatocytes.

Sympathetic drive to liver and nonhepatic splanchnic tissue during heavy exercise

“…Sympathetic innervation of the liver has been proposed to have an important function in the stimulation of hepatic glucose production during exercise on the basis of two premises. First, increases in phosphorylase a activity (9,22) and hepatic glycogenolysis (8,9,14) occur with direct hepatic nerve stimulation. Second, the exercise-induced increase in glucose production is more rapid than changes in arterial glucagon, insulin, and epinephrine levels (7).…”

Possible involvement of eicosanoids in the actions of sympathetic hepatic nerves on carbohydrate metabolism and hemodynamics in perfused rat liver

“…A possible involvement of eicosanoids in nerve action was also indicated by the finding in anaesthetized rabbits in vivo that glycogen phosphorylase activation by preganglionic stimulation of the splanchnic, rather than by postganglionic stimulation of the hepatic nerves, was inhibited by intraperiportal infusion of Indo [34]. Since prostaglandins of the E series were shown to inhibit glucagon-stimulated glycogenolysis and CAMP formation [35,36], the possibility has to be considered that prostaglandins of the F series or thromboxanes may be involved in mediating metabolic nerve action.…”

Neural control and neurosensory functions of the liver

“…There is, however, conflicting evidence from rabbits that neither a-nor P-blockers prevent the phosphorylase activation response to nerve stimulation of the liver and conversely that the response to noradrenaline is blocked by a-blockers (Shimazu & Usami, 1982); unfortunately these authors did not measure blood glucose concentrations. Edwards (1972) showed that the effect of splanchnic stimulation on hepatic glycogenolysis was not modified by adrenalectomy and pancreatectomy, thus supporting direct nervous affects on the liver as being important in addition to indirect effects via adrenalin and pancreatic hormones.…”