Glucocorticoids modulate neurotransmitter-induced glycogen metabolism in cultured cortical astrocytes.
Glucocorticoids (GC) are considered as key modulators of glycogen homeostasis in peripheral tissues, but their role in the central nervous system has only partially been characterized. Exposure of primary cultures of cortical astrocytes to dexamethasone (DEX), a synthetic glucocorticoid, results in the reduction of noradrenaline (NA)-induced glycogen synthesis in a concentration-dependent manner with a IC50 of 4.88 nm and a maximum inhibition of 51%. Such an effect is mediated via glucocorticoid receptors (GRs), since it is mimicked by the glucocorticoid analogue RU28362 (100 nm) and prevented by the GR antagonist RU38486 (1 micro m). DEX does not act through alteration of signal transduction mechanisms, as cAMP formation induced by noradrenergic stimulation was unchanged. Moreover, glycogen synthesis was inhibited to the same extent when DEX was applied either together or only after a brief NA application. Neither [3H]2-deoxyglucose uptake nor lactate release was altered by DEX in the presence of NA, demonstrating that inhibition of glycogen synthesis is not a consequence of reduced glucose utilization or availability. Interestingly, enhancement of glycogen synthase activity induced by NA was reduced in the presence of DEX (-27%). These results suggest that GC could have a significant influence on neuroenergetics as they could modulate activity-related changes in brain glycogen metabolism.
Allaman
Igor
I
Institut de Physiologie, Faculté de Médecine, Université de Lausanne, 1005 Lausanne, Switzerland. igor.allaman@iphysiol.unil.ch
Pellerin
Luc
L
Magistretti
Pierre J
PJ
D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D000242:Cyclic AMP / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology*; D006003:Glycogen / Q000378:metabolism*; D006727:Hormone Antagonists / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D043322:Lactase / Q000378:metabolism; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
D000732:Androstanols; D002352:Carrier Proteins; D005938:Glucocorticoids; D006727:Hormone Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D018377:Neurotransmitter Agents; C104748:Ppp1r3c protein, mouse; D012333:RNA, Messenger; D014316:Tritium; D015735:Mifepristone; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D006003:Glycogen; D003847:Deoxyglucose; D000242:Cyclic AMP; D043322:Lactase; D009638:Norepinephrine