Joseph J Oleynek

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We recently reported the identification of a novel human adenosine A3 receptor-selective agonist, (2S,3S,4R,5R)-3-amino-5-[6-[5-chloro-2-(3-methylisoxazol-5-ylmethoxy)benzylamino]purin-9-yl]-4-hydroxytetrahydrofuran-2-carboxylic acid methylamide (CP-608,039), with 1,260-fold selectivity for the human A3 versus human A1 receptor (DeNinno et al., J Med Chem(More)
Selective adenosine A(3) agonists have potential utility for the prevention of perioperative myocardial ischemic injury. Herein, we report on the discovery and synthesis of compound 7. This amino nucleoside agonist possesses unprecedented levels of selectivity for the human adenosine A(3) receptor.
Lectin-like oxidized LDL (ox-LDL) receptor-1 (LOX-1) is a type-II transmembrane protein that belongs to the C-type lectin family of molecules. LOX-1 acts as a cell surface endocytosis receptor and mediates the recognition and internalization of ox-LDL by vascular endothelial cells. Internalization of ox-LDL by LOX-1 results in a number of pro-atherogenic(More)
There has been considerable difficulty in defining distinct adrenomedullin (AM) binding sites and function in vivo. However, a rat adrenomedullin receptor (rAMR) and a putative human adrenomedullin receptor (hAMR) have recently been reported. We attempted to confirm and extend the pharmacological characterization of these cloned receptors. COS-7 cells(More)
OBJECTIVE The aim of this study was to characterize the adenosine A3 receptor agonist, N6-(3-chlorobenzyl)-5'-N-methylcarboxamidoadenosine (CB-MECA), evaluate its ability to reduce myocardial ischemia/reperfusion injury and determine the role of KATP-channel activation in A3 receptor-mediated cardioprotection. METHODS Binding affinities and adenylate(More)
The mechanisms of pinacidil-induced direct vasodilation were studied in vitro in RMA and RAO. In RMA, pinacidil produced dose-dependent relaxations of norepinephrine (5 microM)-induced contractions with an IC50 of 0.2 microM. This component of pinacidil relaxation appeared to be dependent on K+ conductance because pretreatment with tetraethylammonium (10(More)
The role of adenosine A1 and A3 receptors in mediating cardioprotection has been studied predominantly in rabbits, yet the pharmacological characteristics of rabbit adenosine A1 and A3 receptor subtypes are unknown. Thus, the rabbit adenosine A3 receptor was cloned and expressed, and its pharmacology was compared with that of cloned adenosine A1 receptors.(More)
Although ischemic preconditioning (IP) in several species can be pharmacologically mimicked by selective adenosine A1 or A3 receptor agonists, it is currently unclear which receptor subtype (A1 and/or A3) is physiologically involved in mediating IP. To investigate this question, we determined (a) the affinity of adenosine for rabbit adenosine A1 and A3(More)
This study describes a sensitive in vitro relaxation assay using isolated rabbit mesenteric artery to detect the activity of a vasodilator as a K(+)-channel activator. Thus, comparison of several known K(+)-channel activators was made with other vasodilators known to work via various cellular mechanisms. The vasodilators used were minoxidil sulfate (MNXS; 5(More)
Evidence from contractile, radioisotope ion flux and electrophysiological studies suggest that minoxidil sulfate (MNXS) acts as a K+ channel opener in vascular smooth muscle. This study was designed to examine possible biochemical mechanisms by which MNXS exerts such an effect. Experiments performed in the isolated rabbit mesenteric artery (RMA) showed that(More)