The present study demonstrates the anti-inflammatory effect of adenosine kinase inhibitor (ADKI) in glial cells. Treatment of glial cells with IC51, an ADKI, stimulated the extracellular adenosine release and reduced the LPS/IFNgamma-mediated production of NO, and induction of iNOS and TNF-alpha gene expression. The recovery of IC51-mediated inhibition of iNOS expression by adenosine transport ...

In previous in vivo studies with mice, rats, cats and monkeys, we have demonstrated that [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)- 1,3,7-trimethylxanthine ([11C]TMSX) is a potential radioligand for mapping adenosine A2A receptors of the brain by positron emission tomography (PET). In the present study, we studied the potential of [11C]TMSX for myocardial imaging. Uptake of radioactivity by...

We previously reported that adenosine A2B receptor activation stimulates angiogenesis. Because hypoxia is a potent stimulus for the release of both adenosine and angiogenic factors, we tested the hypothesis that hypoxia alters the expression of adenosine receptors toward an "angiogenic" phenotype. We used human umbilical vein endothelial cells (HUVECs) and bronchial smooth muscle cells (BSMCs) ...

Adenosine A2A receptors and ATP-activated K(+) (KATP) channels contribute to part of the cerebral vasodilatory response to systemic hypoxia, but other mediators are likely involved. Epoxyeicosatrienoic acids (EETs) are cerebral vasodilators and are released from astrocytes exposed to hypoxia. Moreover, stimulation of metabotropic glutamate receptors (mGluR) produces vasodilation by an EET-depen...

The molecular mechanisms of interaction between Gs and the A2A adenosine receptor were investigated using synthetic peptides corresponding to various segments of the Gas carboxyl terminus. Synthetic peptides were tested for their ability to modulate binding of a selective radiolabeled agonist, [H]2-[4-(2-carboxyethyl)phenylethylamino]-59-N-ethylcarboxamidoadenosine ([H]CGS21680), to A2A adenosi...

The endogenous nucleoside adenosine is thought to play a role in the pathophysiology of asthma by stimulating mast cells. We previously showed that the human mast cell line HMC-1 expresses A2A and A2B receptors, and that both receptors activate adenylate cyclase via Gs-protein but that only A2B receptors are also coupled to phospholipase C via Gq proteins. Stimulation of A2B but not A2A recepto...

Adenosine inhibits rat vascular smooth muscle cell (SMC) growth. However, the effects of adenosine on human vascular SMC proliferation and synthesis of extracellular matrix proteins, such as collagen, are unknown. The objective of this study was to characterize the effects of exogenous and endogenous (SMC-derived) adenosine on human aortic SMC proliferation and collagen synthesis. Growth-arrest...

A life-threatening manifestation of Covid-19 infection is a cytokine storm that requires hospitalization and supplemental oxygen. Various strategies to reduce inflammatory cytokines have had some success in limiting improving survival. Agonists adenosine A2A receptors (A2AR) release from most immune cells. Apadenoson potent selective anti-inflammatory analog reduces inflammation. When administe...

Interleukin 12 (IL-12) is a crucial cytokine in the regulation of T helper 1 vs. T helper 2 immune responses. In the present study, we investigated the effect of the endogenous purine nucleoside adenosine on the production of IL-12. In mouse macrophages, adenosine suppressed IL-12 production. Although the order of potency of adenosine receptor agonists suggested the involvement of A2a receptors...

Adenosine, a purine ribonucleoside, exhibits neuromodulatory and neuroprotective effects in the brain and is involved in memory formation and cognitive function. Adenosine signaling is mediated by adenosine receptors (A1, A2A, A2B, and A3); in turn, nucleotide and nucleoside-metabolizing enzymes and adenosine transporters regulate its levels. Scopolamine, a muscarinic cholinergic receptor antag...