Signal transduction pathways and tyrosine hydroxylase regulation in the adrenal medulla following glucoprivation: An in vivo analysis

Larisa Bobrovskaya, Hanafi A. Damanhuri, Lin Kooi Ong, Jennifer J. Schneider, Phillip W. Dickson, Peter R. Dunkley, Ann K. Goodchild*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    22 Citations (Scopus)

    Abstract

    The regulation of tyrosine hydroxylase (TH, the rate limiting enzyme involved in catecholamine synthesis) is critical for the acute and sustained release of catecholamines from adrenal medullary chromaffin cells, however the mechanisms involved have only ever been investigated under in vitro/. in situ conditions. Here we explored the effects on, TH phosphorylation and synthesis, and upstream signalling pathways, in the adrenal medulla evoked by the glucoprivic stimulus, 2-deoxy-d-glucose (2DG) administered intraperitoneally to conscious rats. Our results show that 2DG evoked expected increases in plasma adrenaline and glucose at 20 and 60. min. We demonstrated that protein kinase A (PKA) and cyclin dependent kinases (CDK) were activated 20. min following 2DG, whereas mitogen activated protein kinase (MAPK) was activated later and PKC was not significantly activated. We demonstrated that phosphorylation of Ser40TH peaked after 20. min whereas phosphorylation of Ser31TH was still increasing at 60. min. Serine 19 was not phosphorylated in this time frame. TH phosphorylation also occurred on newly synthesized protein 24. h after 2DG. Thus 2DG increases secretion of adrenaline into the plasma and the consequent rise in glucose levels. In the adrenal medulla 2DG activates PKA, CDK and MAPK, and evokes phosphorylation of Ser40 and Ser31 in the short term and induces TH synthesis in the longer term all of which most likely contribute to increased capacity for the synthesis of adrenaline.

    Original languageEnglish
    Pages (from-to)162-167
    Number of pages6
    JournalNeurochemistry International
    Volume57
    Issue number2
    DOIs
    Publication statusPublished - Sep 2010

    Fingerprint

    Dive into the research topics of 'Signal transduction pathways and tyrosine hydroxylase regulation in the adrenal medulla following glucoprivation: An in vivo analysis'. Together they form a unique fingerprint.

    Cite this