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β1-adrenoceptor-stimulated lactate production in cultured astrocytes is predominantly glycogen-independent.

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journal contribution
posted on 2020-05-28, 13:50 authored by Xianguo Jiang, John Challiss Conceptualisation, Paul Glynn
Noradrenaline (NA) promotes breakdown of the glucose-polymer, glycogen, and hence enhances glycolytic production of lactate in astrocytes. Here, in cultured rat cerebrocortical astrocytes, we examined the contributions of different adrenoceptor subtypes to NA-modulated glucose metabolism, and the relationship of NA-induced glycogenolysis to lactate production. Stimulation of astrocytic glucose metabolism by NA was mediated predominantly via β1-adrenoceptors and cAMP. Constitutive β 1-adrenoceptor activity - in the absence of exogenous NA - contributed to the basal rate of glycogen turnover. Although mRNAs encoding both β 1- and β 2-adrenoceptors were detected in these astrocytes, β 2-adrenoceptors contributed little to NA-induced modulation of glucose metabolism. Activation of α2- and α 1-adrenoceptors in these cells decreased cAMP and increased cytosolic Ca2+, respectively, but did not modulate NA-induced glycogenolysis: α 2-adrenoceptors because glycogenolysis was induced maximally by NA concentrations that only began to inhibit cAMP production; and α 1-adrenoceptors possibly because of desensitisation and depletion of Ca2+ stores. Under basal conditions, astrocytes converted glucose to extracellular lactate in near stoichiometric manner. When glucose-starved astrocytes were given fresh glucose-containing medium, lactate accumulation displayed a brief lag period before attaining a steady-state rate. During this lag period NA, acting at β 1-adrenoceptors, increased the rate of lactate accumulation both in the absence and presence of an inhibitor of glycogen turnover. At the steady-state, the rate of glucose incorporation into accumulated glycogen was ∼5% of that into lactate, but NA enhanced lactate output by 20-50%: this further indicates that NA, via β 1-adrenoceptors and cAMP, can enhance astrocytic lactate production independently of its effect on glycogen turnover.

Funding

These studies were done in partial fulfilment for a PhD degree (for XJ) from the University of Leicester, UK. Support and partial funding for these studies by Renji Hospital, Medical School of Shanghai Jiaotong University, China is gratefully acknowledged.

History

Citation

Biochemical Pharmacology Volume 177, July 2020, 114035

Version

  • AM (Accepted Manuscript)

Published in

Biochemical Pharmacology

Volume

177

Pagination

114035

Publisher

Elsevier BV

issn

0006-2952

eissn

1873-2968

Acceptance date

2020-05-06

Copyright date

2020

Language

eng

Publisher version

https://www.sciencedirect.com/science/article/pii/S0006295220302677

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