Cholinergic stimulation of the lateral hypothalamic neurons with intrahypothalamic microinjections of acetylcholine or carbachol caused a marked increase in the content of the active form of glycogen (starch) synthase in the liver. Total activity of the enzyme (active plus inactive forms) was not increased significantly. The lowest effective dose of acetylcholine was 5 X 10(-10) mole, and the optimum dose was 5 X 10(-9) mole. Similar applications of other neurotransmitters, such as norepinephrine, dopamine, serotonin, and gamma-aminobutyric acid, did not affect the enzyme's activity.

Acetylcholine↗

PubMed1976

Mechanism of lipolysis induced by electrical stimulation of the hypothalamus in the rabbit.

Electrical stimulation of the ventro-medial hypothalamus of the rabbit elevated plasma glycerol concentration. This elevation was suppressed by treatments of the animals with hexamethonium and propranolol, or by adrenalectomy, but was not suppressed by treatments with atropine and phentolamine. These results would indicate that the effect of electrical stimulation of ventro-medial hypothalamus is mainly mediated by catecholamine(s) liberated from the adrenal medulla and acts on beta-receptor of adipose tissue.

Animals↗

PubMed1975

Regulation of glycogen metabolism in liver by the autonomic nervous system. VI. Possible mechanism of phosphorylase activation by the splanchnic nerve.

The effects of autonomic-nerve stimulation on the activities of phosphorylase (EC 2.4.1.1), dephospho-phosphorylase kinase (EC 2.7.1.38) and phosphorylase phosphatase (EC 3.1.3.17), and on the concentration of adenosine 3', 5'-monophosphate in rabbit liver were investiaged. Results were compared with the effects of epinephrine and glucagon on these enzymes. 1. The acitivity of liver phosphorylase increased rapidly and markedly on electrical stimulation of the splanchnic nerve, or after intraportal administration of epinephrine or glucagon. The activity was not affected by vagal stimulation. 2. The activity of dephospho-phosphorylase kinase increased about 2--3-fold 1 min after injections of epinephrine and glucagon, glucagon causing more activation than epinephrine. The enzyme activity was not altered by splanchnic-nerve, or vagal stimulation. 3. Injections of epinephrine and glucagon caused marked elevation of liver adenosine 3', 5'-monophosphate within a few minutes. With epinephrine, the nucleotide concentration rose to a maximum after 1 min and amounted to about 3-fold increase, while with glucagon the maximum increase of approximately 8-fold increase was observed after 2 min. Stimulation of the splanchnic nerve for 10 min did not affect the adenosine 3', 5'-monophosphate level in the liver. Vagal stimulation also had no effect on the level. 4. The activity of phosphorylase phosphatase decreased promptly (within 30 s) and markedly on splanchnic-nerve stimulation, but did not change significantly on administration of epinephrine of glucagon. A small but insignificant increase in phosphatase activity wasobserved upon vagal stimulation. 5. The effect of Ca-2+ on purified dephospho-phosphorylase kinase was studied. The activity was found to depend partially on free Ca-2+ at low Ca-2+ concentrations (1-10-minus 7--1-10-minus 5 M). 6. These results suggest that the rise in hepatic phosphorylase content upon splanchnic-nerve stimulation, unlike that induced by epinephrine and glucagon, is not mediated by adenosine 3', 5'-monophosphate and subsequent activation of dephospho-phosphorylase kinase, but rather by inactivation of phosphorylase phosphatase. The possible existence of a new factor in this mechanism is discussed.

Adenosine Monophosphate↗

PubMed1975

Effects of hypothalamic stimulation on gluconeogenesis and glycolysis in rat liver.

Hypothalamic effects on gluconeogenesis and glycosis in rat liver were studied byelectrical stimulations of the ventromedial hypothalamic nucleus (LH) without disturbing the animal's behavior. Stimulation of VMH caused a increase in the activity of phosphoenolpyruvate carboxykinase (PEPCK), a key gluconeogenic enzyme, and marked suppression of pyruvate kinase (PK), a key glycolytic enzyme, of the liver. Stimulationof LH, on the other hand, resulted in a decrease in PEPCK activity but did not alterPK activity. The maximal responses of these enzymes to hypothalamic stimulations were obtained after intermittent stimulations for 4 h. Differential estimations of thetwo isozymes of liver PK (types L and M) were made using antibody against typeM PK. The level of type M enzyme was not altered significantly on stimulation of either VMH or LH. The content of type L enzyme greatly decreased on stimulation of VMH but was not affected by stimulation of LH. The reciprical influences of VMH and LH on hepatic carbohydrate metabolism and their relation to neural-hormonal responses are discussed.

Animals↗

PubMed1972