Neuropsychopharmacology (2010) 35, 374-387; doi: 10.1038/npp.2009.141; published online 23 September 2009″
“Objective: Endothelial cells express the ectoenzyme ectonucleoside adenosine triphosphate diphosphohydrolase, an apyrase that Cisplatin cost inhibits vascular inflammation by catalyzing the hydrolysis of adenosine triphosphate and adenosine diphosphate. However, ectonucleoside adenosine triphosphate diphosphohydrolase expression is rapidly lost following oxidative stress, leading to the potential for adenosine triphosphate and related purigenic nucleotides to exacerbate acute solid organ

inflammation and injury. We asked if administration of a soluble recombinant apyrase APT102 attenuates lung graft injury in a cold ischemia reperfusion model of rat syngeneic orthotopic lung transplantation.

Methods: Male Fisher 344 donor lungs were cold preserved in a low-potassium

dextrose solution in the presence or absence of APT102 for 18 hours prior to transplantation into syngeneic male Fisher 344 recipients. Seven minutes after reperfusion, lung transplant recipients received either a bolus of APT102 or vehicle (saline solution). Four hours after reperfusion, APT102- and saline solution-treated groups were evaluated for lung graft function and inflammation.

Results: APT102 significantly reduced lung graft extracellular pools of adenosine triphosphate and adenosine diphosphate, improved oxygenation, and protected against pulmonary edema. Apyrase treatment was associated with attenuated neutrophil graft sequestration and less evidence of tissue inflammation as assessed by myeloperoxidase activity, expression buy Acalabrutinib of proinflammatory mediators, and numbers of apoptotic endothelial cells.

Conclusions: Administration of a soluble recombinant apyrase

promotes lung function and limits the tissue damage induced by prolonged cold storage, indicating Baricitinib that extracellular purigenic nucleotides play a key role in promoting ischemia-reperfusion injury following lung transplantation.”
“Rats selectively bred based on high or low reactivity to a novel environment were characterized for other behavioral and neurobiological traits thought to be relevant to addiction vulnerability. The two lines of animals, which differ in their propensity to self-administer drugs, also differ in the value they attribute to cues associated with reward, in impulsive behavior, and in their dopamine system. When a cue was paired with food or cocaine reward bred high-responder rats (bHRs) learned to approach the cue, whereas bred low-responder rats (bLRs) learned to approach the location of food delivery, suggesting that bHRs but not bLRs attributed incentive value to the cue. Moreover, although less impulsive on a measure of ‘impulsive choice’, bHRs were more impulsive on a measure of ‘impulsive action’-ie, they had difficulty withholding an action to receive a reward, indicative of ‘behavioral disinhibition’.