Adenosine A3 receptor activation

Fozard JR, Pfannkuche HJ, Schuurman H-J (1996) Mast cell degranulation following adenosine A3 receptor activation in rats. Eur J Pharmacol 298(3) 293-297 Fredholm BB, Arslan G, Halldner L, Kull B, Schulte G, Wasserman W (2000) Structure and function of adenosine receptors and their genes. Naunyn Schmiedebergs Arch Pharmacol 362(4-5) 364-374 Fredholm BB, IJzerman AP, Jacobson KA, Klotz K-N, Linden J (2001a) International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 53(4) 1-26... 

Das S, Cordis GA, Maulik N, Das DK (2005a) Pharmacological preconditioning with resveratrol role of CREB-dependent Bcl-2 signaling via adenosine A3 receptor activation. Am J Physiol 288(1) H328-H335... 

Sanderson G, Scholfield CN (1986) Effects of adenosine uptake blockers and adenosine on evoked potentials of guinea-pig olfactory cortex. Pflugers Arch 406(l) 25-30 Sattin A, Rail TW (1970) The effect of adenosine and adenine nucleotides on the cyclic adenosine 3, 5 -phosphate content of guinea pig cerebral cortex slices. Mol Pharmacol 6(1) 13-23 Sawynok J, Zarrindast MR, Reid AR, Doak GJ (1997) Adenosine A3 receptor activation produces nociceptive behaviour and edema by release of histamine and 5-hydroxytryptamine. Eur J Pharmacol 333(1) 1-7... 

Philipp S, Yang XM, Cui L, Davis AM, Downey JM, Cohen MV (2006) Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2b receptor cascade. Cardiovasc Res 70(2) 308-314 Platts SH, Duling BR (2004) Adenosine A3 receptor activation modulates the capillary endothelial glycocalyx. Circ Res 94(l) 77-82... 

Given the intense interest on adenosine and adenosine receptor-induced cytoprotec-tive effects, a number of biological models have been developed to study the role of each receptor subtype and to investigate its underlying signaling mechanism. Historically, research on the protective action of adenosine A3 receptors began with protection of the heart from ischemia/reperfusion injury. A growing body of evidence has accumulated to support a cardio-protective effect of adenosine A3 receptor activation. This topic is well-addressed in another chapter in the book, only a brief summary will be described when relevant. 

Maddock HL, Mocanu MM, Yellon DM (2002) Adenosine A3 receptor activation protects the myocardium from reperfusion/reoxygenation injury. Am J Physiol Heart Circ Physiol. 283 H1307-H1313... 

Platts S.H. and Duling B.R. Adenosine A3 receptor activation modulates the capillary endothelial glycocalyx. Circ. Res. 94 77-82, 2004. 

In platelets, depletion of intracellular Ca + reduces 5-HT transport and this points to calmodulin as another endogenous regulator and its antagonists do inhibit 5-HT uptake. In contrast, activation of adenosine (A3) receptors seems to upregulate the transporter, possibly through the PKG, NO/cGGP pathway. 

As described above, a series of 5-pyridylaminothiazoles had been designed and synthesised as highly potent and selective antagonists at the adenosine A3 receptor (Press et al. 2004). It was essentially an extension of the structure-activity relationship to involve 5-imidazo and 5-triazolo substituted aminothiazoles which enabled the rapid identification of several dual A2B/A3 receptor antagonists with acceptable selectivity over the A and A2a receptors. Of the lead compounds, the mesylate salt of 3-[5-(meth-ylimidazol-l-yl)-2-(pyrazin-2-ylamino)-thiazol-4-yl benzonitrile (QAF805) was considered to be the superior compound (Compound 5f - Press et al. 2005). 

Smith SR, Denhardt G, Terminelli C (2002) A role for histamine in cytokine modulation by the adenosine A3 receptor agonist 2-C1-IB-MECA. Eur J Pharmacol 457 57-69 Tilley SL, Wagoner VA, Salvatore CA, Jacobson M, Koller BH (2000) Adenosine and inosine increase cutaneous vasopermeability by activating A(3) receptors on mast cells. J Clin Invest 105 361-367... 

Adenosine A3 receptors have been shown to couple to classical or G protein-dependent second-messenger pathways through activation of both Gi family and Gq family G proteins (Palmer et al. 1995 Merighi et al. 2003 Hasko and Cronstein 2004). 

Besides ERK1/2, there is experimental evidence that adenosine A3 receptors also activate p38 MAPKs in hCHO-A3 cells (Hammarberg et al. 2004). Furthermore, it has been demonstrated that A3 receptor stimulation is able to increase p38 phosphorylation in human hypoxic melanoma, glioblastoma and colon carcinoma cells (Merighi et al. 2005b, 2006, 2007a). 

Resveratrol preconditions the heart through activation of adenosine A3 receptors protecting the heart through a cAMP response element-binding (CREB)-dependent Bcl-2 pathway in addition to an Akt-Bcl-2 pathway (Das et al. 2005a, b). 

Das S, Tosaki A, Bagchi D, Maulik N, Das DK (2005b) Resveratrol-mediated activation of cAMP response element-binding protein through adenosine A3 receptor by Akt-dependent and -independent pathways. J Pharmacol Exp Ther 314(2) 762-769... 

Lee JE, Bokoch G, Liang BT (2001) A novel cardioprotective role of RhoA new signaling mechanism for adenosine. FASEB J 15(11) 1886—1894 Lee JY, Jhun BS, Oh YT, Lee JH, Choe W, Baik HH, Ha J, Yoon KS, Kim SS, Kang I (2006) Activation of adenosine A3 receptor suppresses lipopolysaccharide-induced TNF-alpha production through inhibition of PI3-kinase/Akt and NF-kappaB activation in murine BV2 microglial cells. Neurosci Lett 396(1) 1-6... 

Tracey WR, Magee W, Masamune H, Oleynek JJ, Hill RJ (1998) Selective activation of adenosine A3 receptors with N6-(3-chlorobenzyl)-5 -N-methylcarboxamidoadenosine (Cl-IB-MECA) provides cardioprotection via KATP channel activation. Cardiovasc Res 40( 1) 138—145... 

Zhao TC, Kukreja RC (2002) Late preconditioning elicited by activation of adenosine A3 receptor in heart role of NF- kappa B, iNOS and mitochondrial KATp channel. J Mol Cell Cardiol... 

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