Chemical coding of the hypothalamic neurones in metabolic control. II. Norepinephrine-sensitive neurones and glycogen breakdown in liver

Abstract

Our previous study has demonstrated that acetylcholine-sensitive neurones of the lateral hypothalamic nucleus are specifically concerned in the regulation of liver glycogen synthesis. The present study was undertaken to specify the ventromedial hypothalamic (VMH) neurones involved in regulation of liver glycogen breakdown, by means of chemical stimulation of the VMH with different neurotransmitters. Microinjection of norepinephrine (5 × 10 −10−5 × 10 −8 mol) into the VMH of rats caused a rapid increase in liver phosphorylase-a activity, the active form of this key glycogenolytic enzyme. Focal application of acetylcholine, serotonin, or GABA, on the other hand, did not affect appreciably the enzyme activity. Administration of dopamine into the VMH slightly decreased the phosphorylase-a activity. The effect of noradrenergic stimulation of the VMH on liver phosphorylase was blocked by previous intrahypothalamic application of propranolol, but was not by phentolamine. The effect of norepinephrine was also abolished by previous intraperitoneal injection of hexamethonium. These results indicate that, among other neurones, norepinephrine-sensitive neurones in the VMH are involved in regulation of phosphorylase activity in the liver and the effect of norepinephrine seems to be linked to β-adrenoreceptors in the hypothalamus. They also suggest that a noradrenergic component in the VMH-splanchnic nerve pathway is an important neural regulatory system for hepatic glycogen breakdown.