Norepinephrine: a potent activator of glycogenolysis and gluconeogenesis in rockfish hepatocytes.

Norepinephrine (NOR) is a potent activator of carbohydrate metabolism in isolated hepatocytes from copper rockfish (Sebastes caurinus), increasing rates of glycogenolysis fourfold with an EC50 of 6.3 nM. Nanomolar concentrations of NOR also enhance gluconeogenesis. Epinephrine (EPI) activates both pathways to a smaller extent; the corresponding EC50 for glycogenolysis is 320 nM. There is no significant difference between the magnitude of glucose production in response to comparable doses of NOR, bovine glucagon, and catfish glucagon-like peptide. Experiments with an adrenergic agonist (isoproterenol) and antagonists (propranolol, prazosin, atenolol) indicate that NOR effects are mediated through beta-adrenoceptors. Catecholamine-activated glycogenolysis measured at 100 nM EPI or NOR is poorly correlated with a 30-50% rise in intracellular cAMP. Glucose production following catecholamine administration is not linear: 50% of the hourly glucose output is released within the first 17 min (NOR) and 5 min (EPI), respectively. During hepatocyte incubation (60 min at 15 degrees), added NOR and EPI (100 nM) were not degraded to any significant extent. In the absence of added hormones, rockfish hepatocytes produce 7.41 +/- 0.89 mumol glucose x g-1 packed cells x hr-1 at 15 degrees, with gluconeogenesis accounting for 35.0% of the total production. The rate of glucose output, which is linear for at least 60 min, is not correlated with the initial hepatocyte glycogen level.