Baines, A. E., Corrêa, Sônia A. L., Irving, A. J. and Frenguelli, Bruno G.. (2011) Differential trafficking of adenosine receptors in hippocampal neurons monitored using GFP- and super-ecliptic pHluorin-tagged receptors. Neuropharmacology, Vol.61 (No.1-2). pp. 1-11. ISSN 0028-3908

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Abstract

Adenosine receptors (ARs) modulate many cellular and systems-level processes in the mammalian CNS. However, little is known about the trafficking of ARs in neurons, despite their importance in controlling seizure activity and in neuroprotection in cerebral ischaemia. To address this we examined the agonist-dependent internalisation of C-terminal GFP-tagged A(1)Rs, A(2A)Rs and A(3)Rs in primary hippocampal neurons. Furthermore, we developed a novel super-ecliptic pHluorin (SEP)-tagged AIR which, via the N-terminal SEP tag, reports the cell-surface expression and trafficking of A(1)Rs in real-time. We demonstrate the differential trafficking of ARs in neurons: A(3)Rs internalise more rapidly than A(1)Rs, with little evidence of appreciable A(2A)R trafficking over the time-course of the experiments. Furthermore, the novel SEP-A(1)R construct revealed the time-course of internalisation and recovery of cell-surface expression to occur within minutes of agonist exposure and removal, respectively. These observations highlight the labile nature of A(1)R and A(3)Rs when expressed at the neuronal plasma membrane. Given the high levels of adenosine in the brain during ischaemia and seizures, internalisation of the inhibitory A(1)R may result in hyperexcitability, increased brain damage and the development of chronic epileptic states.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QP Physiology
Divisions:	Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH):	Adenosine -- Receptors, Adenosine -- Receptors -- Physiological transport, G proteins, Neurons
Journal or Publication Title:	Neuropharmacology
Publisher:	Elsevier
ISSN:	0028-3908
Official Date:	July 2011
Volume:	Vol.61
Number:	No.1-2
Page Range:	pp. 1-11
Identification Number:	10.1016/j.neuropharm.2011.02.005
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Medical Research Council (Great Britain) (MRC)
URI:	http://wrap.warwick.ac.uk/id/eprint/38721

Data sourced from Thomson Reuters' Web of Knowledge

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