Co-incubation of equine peripheral blood monocytes with LPS and these agonists resulted in inhibition of TNF-alpha production with a rank order of potency that strongly correlated with HKI-272 cell line their binding affinities
for equine adenosine A(2A) receptors.\n\nResults of experiments performed with one of the adenosine receptor agonists (ATL313) and selective adenosine receptor antagonists confirmed that inhibition of LPS-induced production of TNF-alpha occurred via stimulation of A(2A) receptors. Although incubation of monocytes with IB-MECA, a compound purported to act as an adenosine A(3) receptor agonist, reduced LPS-induced TNF-a production, this effect of IB-MECA was inhibited by the A(2A) selective antagonist ZM241385 but not
by the A(3) receptor antagonist MRS 1220. These results indicate that the adenosine receptor subtype responsible for regulation of LPS-induced cytokine production by equine monocytes is the A(2A) receptor.\n\nTo address the signal transduction mechanism responsible for the anti-inflammatory effects of ATL313 in equine monocytes, production of cAMP was compared in the presence and absence of either the adenosine A2A receptor antagonist ZM241385 or the adenosine A(2B) receptor antagonist MRS1706. In the absence of the antagonists, ATL313 increased production of cAMP; ZM241385 inhibited this effect of ATL313, whereas MRS1706 did not. Furthermore, BI 2536 clinical trial incubation of monocytes with either the stable analogue of cAMP, dibutyryl cAMP, or forskolin, an activator of adenylyl cyclase, also inhibited LPS-induced production of TNF-a production by equine monocytes. Collectively, the results of the current
study indicate that adenosine analogues inhibit LPS-induced production of TNF-alpha by equine monocytes primarily via activation of adenosine A(2A) receptors and do so in a cAMP-dependent manner. The results of this study indicate that Proteasome cleavage stable adenosine analogues that are selective for adenosine A(2A) receptors may be suitable for development as anti-inflammatory drugs in horses. Published by Elsevier B.V.”
“The photoluminescence (PL) characteristics of ordered macroporous europium-doped yttrium oxide (Y(2)O(3):Eu(3+)) particles were investigated. The submicrometer particles were prepared by spray pyrolysis using a mixture of a yttrium and europium nitrate solution and colloidal polystyrene latex (PSL) particles as the precursor. The porous particles exhibited higher PL intensity, quantum efficiency, and red-emission properties than the non-porous particles due to their porous structures.