Chemical coding of the hypothalamic neurones in metabolic control. I. Acetylcholine-sensitive neurones and glycogen synthesis in liver

Abstract

To specify the lateral hypothalamic (LH) neurones concerned with regulation of liver glycogen metabolism, the changes in the activities of liver glycogen synthetase and phosphorylase were analyzed after microinjection of different neurotransmitters 3nto the LH of rats. Cholinergic stimulation of the LH with minute amounts (5 x 10 -9 - 5 × 10 -8mole) of acetylcholine or carbachol resulted in a marked increase of the active form of glycogen synthetase, but it did not affect the phosphorylase activity. Total activity of glycogen synthetase (active plus inactive forms) was not increased significantly, indicating that the effect of cholinergic stimulation was due to activation of the enzyme. Noradrenergic, dopaminergic, serotonergic and GABAergic stimulations of the LH, on the other hand, did not affect appreciably the activities of glycogen synthetase and phosphorylase in the liver. The effect of cholinergic stimulation of the LH on liver glycogen synthetase was blocked by previous intrahypothalamic microinjection of anticholinergic agents, such as atropine and scopolamine, or by previous intraperitoneal injection of N-methylatropine or hexamethonium. These results suggest that, among other neurones, cetylcholine-sensitive neurones in the LH are specifically concerned with regulation of glycogen synthetase, and that the cholinergic system in an LH-vagal pathway mediates the neural regulation of glycogen synthesis in the liver.