title: α₂-Adrenoceptors activate noradrenaline-mediated glycogen turnover in chick astrocytes.
abstract: In the brain, glycogen is primarily stored in astrocytes where it is regulated by several hormones/neurotransmitters, including noradrenaline that controls glycogen breakdown (in the short term) and synthesis. Here, we have examined the adrenoceptor (AR) subtype that mediates the glycogenic effect of noradrenaline in chick primary astrocytes by the measurement of glycogen turnover (total (14) C incorporation of glucose into glycogen) following noradrenergic activation. Noradrenaline and insulin increased glycogen turnover in a concentration-dependent manner. The effect of noradrenaline was mimicked by stimulation of α(2) -ARs (and to a lesser degree by β(3) -ARs), but not by stimulation of α(1) -, β(1) -, or β(2) -ARs, and occurred only in astrocytes and not neurons. In chick astrocytes, studies using RT-PCR and radioligand binding showed that α(2A) - and α(2C) -AR mRNA and protein were present. α(2) -AR- or insulin-mediated glycogen turnover was inhibited by phosphatidylinositol-3 kinase inhibitors, and both insulin and clonidine caused phosphorylation of Akt and glycogen synthase kinase-3 in chick astrocytes. α(2) -AR but not insulin-mediated glycogen turnover was inhibited by pertussis toxin pre-treatment indicating involvement of Gi/o proteins. These results show that the increase in glycogen turnover caused by noradrenaline is because of activation of α(2) -ARs that increase glycogen turnover in astrocytes utilizing a Gi/o-PI3K pathway.
authors: Department of Pharmacology, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, 399 Royal Parade, Parkville, Victoria 3052, Australia. dana.hutchinson@monash.edu
authors: Dana S
authors: DS
authors: Hutchinson
authors: Stephanie L
authors: SL
authors: Catus
authors: Jon
authors: J
authors: Merlin
authors: Roger J
authors: RJ
authors: Summers
authors: Marie E
authors: ME
authors: Gibbs
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001711:Biotransformation; D002478:Cells, Cultured; D002642:Chick Embryo; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007700:Kinetics; D009638:Norepinephrine / Q000502:physiology*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation; D016548:Prosencephalon / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012265:Ribonucleotides / Q000494:pharmacology; D015016:Yohimbine
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D007004:Hypoglycemic Agents; D018341:Receptors, Adrenergic, alpha-2; D012265:Ribonucleotides; D015016:Yohimbine; D000620:Aminoimidazole Carboxamide; D006003:Glycogen; D051058:Oncogene Protein v-akt; D038362:Glycogen Synthase Kinase 3; C031143:AICA ribonucleotide; D005947:Glucose; D009638:Norepinephrine