BACKGROUND Similarities between naturally occurring sleep and general anesthesia suggest that the two states may interact physiologically. The authors have previously demonstrated that sleep deprivation potentiates anesthetic-induced loss of righting reflex (LORR) in rats. One possible mediator for this effect is adenosine, which accumulates in the brains of sleep-deprived animals and reduces a...

Adenosine-induced modulation of neuromuscular transmission in young (3-4-week-old) rats was evaluated. Inhibition of adenosine kinase with iodotubercidin (ITU; 10 microM), which is known to induce adenosine release, enhanced the amplitude of evoked end-plate potentials (EPPs) recorded from innervated diaphragm muscle fibers. This facilitatory effect was transformed into an inhibitory one upon b...

Although adenosine has been implicated in penile erection in human males, the receptor subtype responsible for adenosine regulation of human corpus cavernosum (HCC) smooth muscle tone is still a matter of debate. Using selective adenosine agonists and antagonists, we aimed at characterizing the adenosine receptors mediating relaxation of precontracted (with 1 microM phenylephrine) HCC strips. H...

PURPOSE The role of adenosine receptor (AdoR) antagonists in human retinal endothelial cell function in vitro has previously been determined. In this study, efficacy of AdoR antagonist administration in reducing retinal neovascularization was examined in a mouse pup model of oxygen-induced retinopathy. METHODS A previously described model of oxygen-induced retinal neovascularization in newbor...

The human adenosine A(2B) receptor belongs to class A G protein-coupled receptors (GPCRs). In our previous work, constitutively active mutant (CAM) human adenosine A(2B) receptors were identified from a random mutation bank. In the current study, three known A(2B) receptor antagonists, 4-{2-[7-amino-2-(2-furyl)[1,2,4]triazolo-[2,3-a][1,3,5]triazin-5-yl-amino]ethyl}phenol (ZM241385), 8-cyclopent...

Adenosine A(2A) receptors seem to exist in typical (more in striatum) and atypical (more in hippocampus and cortex) subtypes. In the present study, we investigated the affinity of two adenosine A(2A) receptor antagonists, ST1535 [2 butyl -9-methyl-8-(2H-1,2,3-triazol 2-yl)-9H-purin-6-xylamine] and KW6002 [(E)-1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6,dione] to the "...

The function of G-protein-coupled receptors is tightly modulated by the lipid environment. Long-timescale molecular dynamics simulations (totaling approximately 3 mus) of the A(2A) receptor in cholesterol-free bilayers, with and without the antagonist ZM241385 bound, demonstrate the instability of helix II in the apo receptor in cholesterol-poor membrane regions. We directly observe that the ef...

GPCRs regulate all aspects of human physiology, and biophysical studies have deepened our understanding of GPCR conformational regulation by different ligands. Yet there is no experimental evidence for how sidechain dynamics control allosteric transitions between GPCR conformations. To address this deficit, we generated samples of a wild-type GPCR (A2AR) that are deuterated apart from 1H/13C NM...