Adenosine A1 receptor blockade reverses dysmotility induced by ischemia-reperfusion in rat colon

被引:16
作者
Kadowaki, M [1 ]
Tokita, K [1 ]
Nagakura, Y [1 ]
Takeda, M [1 ]
Hanaoka, K [1 ]
Tomoi, M [1 ]
机构
[1] Fujisawa Pharmaceut Co Ltd, Pharmacol Res Labs, Osaka 5320031, Japan
关键词
dysmotility; ischemia-reperfusion; colon; (rat); adenosine A(1) receptor antagonist; RT-PCR (reverse transcription-polymerase chain reaction);
D O I
10.1016/S0014-2999(00)00867-0
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
This study was designed to assess whether adenosine A(1) receptor antagonists [(R)-1-[(E)-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl) acryloyl]-piperidin-2-yl acetic acid (FK352) and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX)] reverse dysmotility induced by ischemia-reperfusion in the rat colon. The gene of adenosine A(1) receptor was expressed in the colon. Clamping (30 min) of the colonic marginal vessels was followed by reperfusion, and the propulsive colonic motility was evaluated. Propulsion was significantly slowed by ischemia-reperfusion, while FK352 and DPCPX abolished this delay. In contrast, the non-selective adenosine receptor antagonist, 8-phenyltheophylline, failed to affect the dysmotility. Thus, adenosine A(1) receptor antagonists have potent therapeutic potential against ischemia-reperfusion-induced dysmotility in the colon. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:319 / 323
页数:5
相关论文
共 14 条
[1]   Ischemia-reperfusion-induced delay in intestinal transit - Role of endothelins [J].
Alican, I ;
Yegen, C ;
Olcay, A ;
Kurtel, H ;
Yegen, BC .
DIGESTION, 1998, 59 (04) :343-348
[2]   EFFECTS OF PURINES ON THE LONGITUDINAL MUSCLE OF THE RAT COLON [J].
BAILEY, SJ ;
HOURANI, SMO .
BRITISH JOURNAL OF PHARMACOLOGY, 1992, 105 (04) :885-892
[3]   Intestinal motility during hypoxia and reoxygenation in vitro [J].
Bielefeldt, K ;
Conklin, JL .
DIGESTIVE DISEASES AND SCIENCES, 1997, 42 (05) :878-884
[4]   PRESYNAPTIC INHIBITION BY ADENOSINE-A1-RECEPTORS ON GUINEA-PIG SMALL INTESTINAL MYENTERIC NEURONS [J].
CHRISTOFI, FL ;
WOOD, JD .
GASTROENTEROLOGY, 1993, 104 (05) :1420-1429
[5]   Depressant effects of hypoxia and hypoglycaemia on neuro-effector transmission of guinea-pig intestine studied in vitro with a pharmacological model [J].
Corbett, AD ;
Lees, GM .
BRITISH JOURNAL OF PHARMACOLOGY, 1997, 120 (01) :107-115
[6]   Tissue distribution of adenosine receptor mRNAs in the rat [J].
Dixon, AK ;
Gubitz, AK ;
Sirinathsinghji, DJS ;
Richardson, PJ ;
Freeman, TC .
BRITISH JOURNAL OF PHARMACOLOGY, 1996, 118 (06) :1461-1468
[7]   Colonic ischemia [J].
Greenwald, DA ;
Brandt, LJ .
JOURNAL OF CLINICAL GASTROENTEROLOGY, 1998, 27 (02) :122-128
[8]   Molecular and functional contractile sequelae of rat intestinal ischemia/reperfusion injury [J].
Hierholzer, C ;
Kalff, JC ;
Audolfsson, G ;
Billiar, TR ;
Tweardy, DJ ;
Bauer, AJ .
TRANSPLANTATION, 1999, 68 (09) :1244-1254
[9]   Molecular identification and pharmacological characterization of adenosine receptors in the guinea-pig colon [J].
Kadowaki, M ;
Takeda, M ;
Tokita, K ;
Hanaoka, K ;
Tomoi, M .
BRITISH JOURNAL OF PHARMACOLOGY, 2000, 129 (05) :871-876
[10]   Species differences in brain adenosine A(1) receptor pharmacology revealed by use of xanthine and pyrazolopyridine based antagonists [J].
Maemoto, T ;
Finlayson, K ;
Olverman, HJ ;
Akahane, A ;
Horton, RW ;
Butcher, SP .
BRITISH JOURNAL OF PHARMACOLOGY, 1997, 122 (06) :1202-1208