Adenosine A1-A2A receptor heteromers: new targets for caffeine in the brain

Abstract

The contribution of blockade of adenosine A1 and A2A receptor to the psychostimulant effects of caffeine is still a matter of debate. When analyzing motor activity in rats, acutely administered caffeine shows a profile of a non-selective adenosine receptor antagonist, although with preferential A1 receptor antagonism. On the other hand, tolerance to the effects of A1 receptor blockade seems to be mostly responsible for the tolerance to the motor-activating effects of caffeine, while the residual motor-activating effects of caffeine in tolerant individuals seem to involve A2A receptor blockade. These behavioral studies correlate with in vivo microdialysis experiments that suggest that A1 receptor-mediated modulation of striatal glutamate release is involved in the psychostimulant effects of caffeine. Experiments in transfected cells demonstrate the ability of A1 receptors to heteromerize with A2A receptors and the A1-A2A receptor heteromer can be biochemically identified in the striatum, in striatal glutamatergic terminals. The striatal A1-A2A receptor heteromer provides a "concentration-dependent switch" mechanism by which low and high concentrations of synaptic adenosine produce the opposite effects on glutamate release. The analysis of the function of A1-A2A receptor heteromers during chronic treatment with caffeine gives new clues about the well-known phenomenon of tolerance to the psychostimulant effects of caffeine.

The Potential Effect of Caffeine and Nicotine Co-administration against Aluminum-induced Alzheimer's disease in Rats

“…It is known that, caffeine can immediately facilitate the release of serotoninergic and dopaminergic transmissions which contribute to antidepressant effects [49]. Caffeine-treated rats also showed insignificant changes in escape latency and time spent in the target quadrant as compared to AlCl 3 group in the MWM indicating non-improvement in learning and memory impairment induced by AlCl 3 .…”

Modulation of Adenosine Receptors by [60]Fullerene Hydrosoluble Derivative in SK-N-MC Cells

“…44 It is well-known the cross-talking between the two types of adenosine receptors studied here, including the formation of heterodimers complexes between A 1 and A 2A receptors. 45,46 We have previously reported the modulation of A 1 and A 2A receptors during hypoxia in an in vitro model of C6 glioma cells culture, where tonic activation of A 1 by endogenous released adenosine promotes modulation on A 1 receptors but on A 2A levels as well. 47 A similar mechanism could take place after fullerene derivative treatment, promoting changes on receptor densities through postreceptor processes.…”

Die adenosien A₁- en A_2A-reseptoraffiniteit van ’n reeks 3,4-dihidropirimidoon-analoë

“…Boonop is daar opgemerk dat pasiënte met Parkinson se siekte, wat gereeld koffie drink, minder kenmerkende simptome toon, gemeet teenoor diegene met Parkinson se siekte wat nie koffie drink nie (Ross et al 2000;Ascherio et al 2001). Kafeïen kom natuurlik voor in koffie en word geklassifiseer as 'n nieselektiewe antagonis van die adenosien A 1 -en A 2A -reseptore (Ferre et al 2008). Die kognitiewe effekte van kafeïen kan merendeels toegeskryf word aan sy vermoë om adenosien A 1 -reseptore in die hippokampus en prefrontale korteks van die brein te antagoniseer (Ribeiro & Sebastião 2010).…”