Although CRT0066101 order both radioligands showed high in vitro specific binding to rat brain slices, their binding characteristics were quite different from each other. 5-Ethyl-[C-11]4HQ (5Et-[C-11]4HQ) showed higher in vitro binding in the forebrain regions than in the cerebellum, bindings that were strongly inhibited by both glycine-site
agonists and antagonists. In contrast, 5-iodo-[C-11]4HQ (5I-[C-11]4HQ) showed a homogeneous in vitro binding throughout the brain, which was inhibited by antagonists but not by agonists. This difference in in vitro binding between 5Et-[C-11]4HQ and 5I-[C-11]4HQ was quite similar to that previously observed between [C-11]L-703,717 and [C-11]4HQ, both glycine-site antagonists. In vivo brain uptakes of these C-11-labeled 4-hydroxyquinolones were examined in mice. Initial brain uptakes Selleck AS1842856 of 5Et- and 5I-[C-11]4HQ at 1 min after intravenous injections were comparable to that of [C-11]4HQ, but they were 1.3-2.1 times higher than
that of [C-11]L-703,717. The treatment with an anticoagulant, warfarin, only slightly increased the initial uptakes of [C-11]4HQ and 5Et-[C-11]4HQ in contrast to [C-11]L-703,717. The in vivo regional brain distributions were slightly different between the two radioligands. Pretreatment with nonradioactive ligand (2 mg/kg) slightly inhibited the binding of 5Et-[C-11]4HQ (16-36% inhibition) but not that of 5I-[C-11]4HQ.
In this study, it was found that a small structural change in [C-11]4HQ resulted in a major change in binding characteristics and distributions, suggesting the existence of two binding
sites for [C-11]4-hydroxyquinolones on the NMDA ion channel-agonist-sensitive and agonist-insensitive (or antagonist-preferring) sites. (c) 2008 Elsevier Inc. All rights reserved.”
“Objective: Adenosine A(2A) receptor activation during reperfusion improves lung ischemia- reperfusion injury. In this study we sought to determine whether pretreatment of rabbits with a potent and selective adenosine A(2A) receptor agonist, ATL-313, before transplantation or whether adding ATL-313 MK-4827 to the preservation solution results in equivalent or additional protection compared with ATL-313 added during reperfusion.
Methods: An isolated, ventilated, ex vivo blood-perfused rabbit lung model was used. All groups underwent 2 hours of reperfusion after 18 hours of cold ischemia (4 C). ATL-313 was administered 1 hour before ischemia intravenously, with the preservation solution, and/or during reperfusion.
Results: Both pretreatment of donor animals with ATL-313 or adding ATL-313 just during reperfusion improved pulmonary function, but significantly greater improvement was observed when pretreatment and treatment during reperfusion were combined (all P < .05).