Pier Andrea Borea

Novel selective antagonist radioligands for the pharmacological study of A2B adenosine receptors

The adenosine A2B receptor is the least well characterized of the four adenosine subtypes due to the lack of potent and selective agonists and antagonists. Despite the widespread distribution of A2B receptor mRNA, little information is available with regard to their function. The characterization of A2B receptors, through radioligand binding studies, has been performed, until now, by using low-affinity and non-selective antagonists like 1,3-dipropyl-8-cyclopentylxanthine ([3H]DPCPX),(4-(2-[7-amino-2-(2-furyl)-[1,2,4]triazolo-[2,3-a][1,3,5]triazin-5-ylamino]ethyl)-phenol ([3H]ZM 241385) and 3-(3,4-aminobenzyl)-8-(4-oxyacetate)phenyl-1-propyl-xanthine ([125I]ABOPX). Recently, high-affinity radioligands for A2B receptors, [N-(4-cyanophenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)-phenoxy]acetamide ([3H]MRS 1754), N-(2-(2-Phenyl-6-[4-(2,2,3,3-tetratritrio-3-phenylpropyl)-piperazine-1-carbonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-ethyl)-acetamide ([3H]OSIP339391) and N-benzo[1,3]dioxol-5-yl-2-[5-(1,3-dipropyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)-1-methyl-1H-pyrazol-3-yloxy]-acetamide] ([3H]MRE 2029F20), have been introduced. This minireview offers an overview of these recently developed radioligands and the most important applications of drugs towards A2B receptors.

A3 Adenosine Receptors, HIF-1 Modulation and Atherosclerosis

Atherosclerosis, a multifactorial disease of the large arteries, is the major cause of heart disease and stroke worldwide. Epidemiological studies have discovered several relevant environmental and genetic risk factors associated with this pathology. Genomic and proteomic-based strategies in humans and rodent models have been instrumental in discovering genes and proteins involved in the initiation and progression of atherosclerosis. Moreover multiple genome-wide approaches are underway to identify variants in the human genome that predispose to, or protect from, cardiovascular disease. Our views of the pathophysiology of atherosclerosis have evolved substantively over the past century and now it is recognized that inflammation and angiogenesis are important features in atherosclerotic plaque development and destabilization. The clinical complications of atherosclerosis are caused by thrombus formation, which in turn results from rupture of an unstable atherosclerotic plaque.