A programmable ligand display system can be used to dissect the multivalent effects of ligand binding to a membrane receptor. An antagonist of the A2A adenosine receptor, a G-protein-coupled receptor that is a drug target for neurodegenerative conditions, was displayed in 35 different multivalent configurations, and binding to A2A was determined. A theoretical model based on statistical mechani...

The formation of new lymphatic vessels, or lymphangiogenesis, is a natural process involved in tissue repair and in the resolution of inflammatory reactions. In some cancers, this process is exploited by the tumor to promote its growth and its metastatic dissemination. Our group recently identified a role for the CD73-adenosine pathway in tumor angiogenesis. As angiogenesis and lymphangiogenesi...

There is mounting evidence that the neuropeptide oxytocin is a possible candidate for the treatment of drug addiction. Oxytocin was shown to reduce methamphetamine self-administration, conditioned place-preference, hyperactivity and reinstatement in rodents, highlighting its potential for the management of methamphetamine addiction. Thus, we hypothesised that the central endogenous oxytocinergi...

Chronic sleep restriction induces blood-brain barrier disruption and increases pro-inflammatory mediators in rodents. Those inflammatory mediators may modulate the blood-brain barrier and constitute a link between sleep loss and blood-brain barrier physiology. We propose that adenosine action on its A2A receptor may be modulating the blood-brain barrier dynamics in sleep-restricted rats. We adm...

Evidence suggests that adenosine (AD) is an endogenous sleep factor. The hypnogenic action of AD is mediated through its inhibitory A1 and excitatory A2A receptors. Although AD is thought to be predominantly active in the wake-active region of the basal forebrain (BF), a hypnogenic action of AD has been demonstrated in several other brain areas, including the preoptic area. We hypothesized that...

Caffeine is the most consumed psychoactive drug in the world. It is a non-selective adenosine receptor antagonist that in the brain targets mainly adenosine A1 and A2A receptors. The same as classical psychostimulants, caffeine produces motor-activating, reinforcing and arousing effects. This depends on the ability of caffeine to counteract multiple effects of adenosine in the central ascending...

Recent studies of G protein-coupled receptors have highlighted two "new" and interactive elements involved in their function and regulation: their ability to localize to different cell surface and intracellular compartments and their ability to interact with partners other than their classic heterotrimeric G proteins. The effects mediated by these receptors can be markedly different depending o...

a2-Adrenergic receptors (ARs) play a key role in regulating neurotransmitter release in the central and peripheral sympathetic nervous systems. To date, three subtypes of a2-ARs have been cloned (a2A, a2B, and a2C). Here we describe the physiological consequences of disrupting the gene for the a2AAR. Mice lacking functional a2A subtypes were compared with wild-type (WT) mice, with animals lacki...

Neurology 2012;79:616–618 Caffeine, the world’s most widely used psychomotor stimulant, potentiates the antiparkinsonian effects of levodopa in preclinical models, as noted nearly 40 years ago.1 The findings prompted early placebo-controlled crossover studies of caffeine as an adjunct to levodopa or a dopamine agonist in Parkinson disease (PD).2,3 No motor effect of caffeine was demonstrated ot...

Background Long-term use of levodopa (l-dopa) is inevitably complicated with highly disabling fluctuations and drug-induced dyskinesias, which pose major challenges to the existing drug therapy of Parkinson's disease. Methods In this study, we conducted a systematic review and meta-analysis to assess the efficacy of A2A receptor antagonists on reducing l-dopa-induced dyskinesias (LID). Resu...