Abstract |
Adenosine protects against cellular damage and dysfunction under several adverse conditions including inflammation and ischemia. In this study, we examined the effects of 3-[1-(6,7-diethoxy-2-morpholinoquinazolin-4-yl)piperidin-4-yl]-1,6-dimethyl-2,4(1H,3H)- quinazolinedione hydrochloride ( KF24345), an adenosine uptake inhibitor, on experimental acute pancreatitis induced by choline-deficient and ethionine-supplemented diet in mice. KF24345, administered with the diet onset and every 24 h thereafter, prevented hyperamylasemia, acinar cell injury and serum tumor necrosis factor-alpha elevation and ultimately decreased mortality. Therapeutic treatment with KF24345, which started 32 h after the diet onset, also decreased mortality. The beneficial effect of KF24345 on mortality was abolished by the pretreatment with 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl) phenol ( ZM 241385), a selective adenosine A(2A) receptor antagonist. An intravenous injection of KF24345 at 48 h after the diet onset increased plasma adenosine concentrations in mice with acute pancreatitis. These results suggest that KF24345 shows anti- pancreatitis effects via endogenous adenosine and adenosine A(2A) receptors. The adenosine uptake inhibition could be a new therapeutic approach for acute pancreatitis.
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Authors | Tohru Noji, Ken-ichiro Nan-ya, Mirai Mizutani, Chikako Katagiri, Jun-ichi Sano, Chie Takada, Satoshi Nishikawa, Akira Karasawa, Hideaki Kusaka |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 454
Issue 1
Pg. 85-93
(Nov 01 2002)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 12409009
(Publication Type: Journal Article)
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Chemical References |
- 3-(1-(6,7-diethoxy-2-morpholinoquinazolin-4-yl)piperidin-4-yl)-1,6-dimethyl-2,4-(1H,3H)-quinazolinedione
- Neurotransmitter Uptake Inhibitors
- Pyrimidinones
- Quinazolines
- Tumor Necrosis Factor-alpha
- L-Lactate Dehydrogenase
- Amylases
- Adenosine
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Topics |
- Acute Disease
- Adenosine
(antagonists & inhibitors, blood)
- Amylases
(blood)
- Animals
- Choline Deficiency
(complications)
- Diet
- Female
- L-Lactate Dehydrogenase
(blood)
- Mice
- Neurotransmitter Uptake Inhibitors
(pharmacology)
- Organ Size
- Pancreas
(drug effects)
- Pancreatitis
(drug therapy, etiology, mortality)
- Pyrimidinones
(pharmacology)
- Quinazolines
(pharmacology)
- Time Factors
- Tumor Necrosis Factor-alpha
(metabolism)
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