Monoamine transmitter activity in lateral hypothalamus during its perfusion with insulin or 2-DG in sated and fasted rat. 1988

R D Myers, and J M Peinado, and F J Miñano
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27857.

A unique profile of neurochemical events is proposed to occur in the diencephalon which is contingent upon the nutrient status of the animal. In this first of a series of investigations, we selected the lateral hypothalamus (LH) in order to determine its specific resting profile of monoaminergic neurotransmitters and their principal metabolites. The neuronal pattern of activity was studied during sated and fasted conditions as well as during a local glucoprivic challenge to the LH. After permanent guide cannulae for push-pull perfusion were implanted in female Sprague-Dawley rats, the LH was perfused repeatedly with an artificial CSF, at a rate of 20 microliters/min, in order to collect a series of 5.0 min samples. Aliquots of each perfusate were assayed directly using a high performance liquid chromatography system with electrochemical detection (HPLC-EC) for pg/microliter concentrations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT). In comparison to the basal levels of amines during the sated condition, when the rat was food-deprived for 20-22 hr, the release of NE, DA, and 5-HT was significantly lower than that observed under the sated condition. Further, the turnover of NE in the LH was concurrently attenuated as reflected by the lower levels of MHPG in the perfusate, thus demonstrating the modification in catecholamine activity produced in the LH by the condition of hunger. When either 10 micrograms/microliters 2-deoxy-D-glucose (2-DG) or 4.0 mU/microliter insulin was incorporated into the CSF perfused in the LH, the efflux of DA was significantly enhanced independent of the state of satiation. In addition, the proportion of both NE and DA to 5-HT was likewise increased by either of these centrally acting substances, while the turnover of 5-HT was enhanced and NE and DA turnovers were reduced. Perfusion of 2-DG in the LH of the fasted rat caused a significant reduction in catecholamine turnover in terms of MHPG/NE, VMA/NE, DOPAC/DA and HVA/DA ratios. Moreover, 2-DG increased NE/5-HT while lowering the NE/DA ratio, and enhanced simultaneously the 5-HTOL/5-HT ratio. In the sated rat, 2-DG attenuated the release of 5-HT from the animal's LH, whereas insulin caused a shift in the proportions of NE/5-HT and DA/5-HT. Further, the peptide served to reduced the efflux of 5-HT, enhanced the turnover of 5-HT while diminishing DA turnover, and shifted the metabolism of NE from MHPG to VMA.(ABSTRACT TRUNCATED AT 400 WORDS)

UI MeSH Term Description Entries
D007026 Hypothalamic Area, Lateral Area in the hypothalamus bounded medially by the mammillothalamic tract and the anterior column of the FORNIX (BRAIN). The medial edge of the INTERNAL CAPSULE and the subthalamic region form its lateral boundary. It contains the lateral hypothalamic nucleus, tuberomammillary nucleus, lateral tuberal nuclei, and fibers of the MEDIAL FOREBRAIN BUNDLE. Lateral Hypothalamic Area,Lateral Hypothalamic Nucleus,Tuberomammillary Nucleus,Accessory Nucleus of the Ventral Horn,Area Hypothalamica Lateralis,Area Lateralis Hypothalami,Lateral Hypothalamus,Lateral Tuberal Nuclei,Lateral Tuberal Nucleus,Area Hypothalamica Laterali,Area Lateralis Hypothalamus,Area, Lateral Hypothalamic,Areas, Lateral Hypothalamic,Hypothalami, Area Lateralis,Hypothalamic Areas, Lateral,Hypothalamic Nucleus, Lateral,Hypothalamica Laterali, Area,Hypothalamica Lateralis, Area,Hypothalamus, Area Lateralis,Hypothalamus, Lateral,Lateral Hypothalamic Areas,Laterali, Area Hypothalamica,Lateralis Hypothalami, Area,Lateralis Hypothalamus, Area,Lateralis, Area Hypothalamica,Nuclei, Lateral Tuberal,Nucleus, Lateral Hypothalamic,Nucleus, Lateral Tuberal,Nucleus, Tuberomammillary,Tuberal Nuclei, Lateral,Tuberal Nucleus, Lateral
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D011972 Receptor, Insulin A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE. Insulin Receptor,Insulin Receptor Protein-Tyrosine Kinase,Insulin Receptor alpha Subunit,Insulin Receptor beta Subunit,Insulin Receptor alpha Chain,Insulin Receptor beta Chain,Insulin-Dependent Tyrosine Protein Kinase,Receptors, Insulin,Insulin Receptor Protein Tyrosine Kinase,Insulin Receptors
D001786 Blood Glucose Glucose in blood. Blood Sugar,Glucose, Blood,Sugar, Blood
D001931 Brain Mapping Imaging techniques used to colocalize sites of brain functions or physiological activity with brain structures. Brain Electrical Activity Mapping,Functional Cerebral Localization,Topographic Brain Mapping,Brain Mapping, Topographic,Functional Cerebral Localizations,Mapping, Brain,Mapping, Topographic Brain
D004435 Eating The consumption of edible substances. Dietary Intake,Feed Intake,Food Intake,Macronutrient Intake,Micronutrient Intake,Nutrient Intake,Nutritional Intake,Ingestion,Dietary Intakes,Feed Intakes,Intake, Dietary,Intake, Feed,Intake, Food,Intake, Macronutrient,Intake, Micronutrient,Intake, Nutrient,Intake, Nutritional,Macronutrient Intakes,Micronutrient Intakes,Nutrient Intakes,Nutritional Intakes
D005260 Female Females
D006815 Hunger The desire for FOOD generated by a sensation arising from the lack of food in the STOMACH.

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