Klyuch, Boris P., Dale, Nicholas and Wall, Mark J.. (2012) Receptor-mediated modulation of activity-dependent adenosine release in rat cerebellum. Neuropharmacology, Vol.62 (No.2). pp. 815-824. ISSN 0028-3908

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Abstract

Although the neuromodulator adenosine plays an important role in many central nervous system physiological and pathological processes, the properties and mechanisms of extracellular adenosine production are still unclear. In previous work, we determined that two forms of adenosine release can be evoked in the molecular layer of the cerebellum: one independent of ionotropic glutamate receptor activation (evoked by a train of stimuli) and one mainly dependent on the activation of ionotropic glutamate receptors (evoked by a single stimulus in 4-aminopyridine). Here we have investigated how these different forms of adenosine release are modulated by metabotropic receptors (A1, GABAB and mGlu4). Although both types of adenosine release are inhibited by the activation of metabotropic receptors, single stimulus-evoked release was much more potently inhibited suggesting differential coupling between receptors and adenosine release mechanisms. Metabotropic receptor antagonists revealed that endogenous A1 receptor activation plays the major role in controlling adenosine release and determine the relationship between stimulus strength and adenosine release. The major mechanism of modulation is through control of ionotropic glutamate receptor activation with block of metabotropic receptors inducing glutamate receptor-dependent adenosine release. In contrast to metabotropic receptor agonists, which inhibit adenylyl cyclase, activation of adenylyl cyclase (with forskolin) increased both glutamate receptor-dependent and independent adenosine release. This is the first time that the control of adenosine release by endogenous modulators has been studied and like classical neurotransmitters, adenosine release is controlled by an interplay of presynaptic modulators.

Item Type:	Journal Article
Divisions:	Faculty of Science > Life Sciences (2010- )
Journal or Publication Title:	Neuropharmacology
Publisher:	Elsevier BV
ISSN:	0028-3908
Date:	February 2012
Volume:	Vol.62
Number:	No.2
Page Range:	pp. 815-824
Identification Number:	10.1016/j.neuropharm.2011.09.007
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
URI:	http://wrap.warwick.ac.uk/id/eprint/41214

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