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

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Abstract
The mechanism of activation of liver phosphorylase after splanchnic nerve stimulation was investigated in rabbits and compared with the effects of intraportal injections of noradrenaline [norepinephrine]. The increase in the activity of liver phosphorylase-.alpha., the active form of this key glycogenolytic enzyme, in reponse to injections of noradrenaline was blocked by .beta.-adrenergic antagonists, but not by .alpha.-adrenergic antagonists, suggesting that the effect of noradrenaline is mediated mainly through .beta.-adrenoceptors in vivo. The increase in phosphorylase activity in response to stimulation of the peripheral end of the splanchnic nerve was resistant to both .alpha.- and .beta.-adrenoceptor blockade. When diltiazem and verapamil, selective Ca2+ antagonists that restrict Ca infux across the cell membrane, were infused intraportally, the phosphorylase response to splanchnic nerve was virtually abolished, while the response to noradrenaline was unaltered. Infusion of the prostaglandin-synthesis inhibitor indomethacin at a dose of 3.4 .mu.g/min blocked the activation of liver phosphorylase in response to stimulation of the splanchnic innervation. The mechanism whereby stimulation of the sympathetic innervation to the liver leads to activation of phosphorylase is not mediated by either .alpha.- or .beta.-adrenoceptors but appears to depend upon prostaglandin formation and infux of Ca2+ into the hepatocytes.