Adenosine A1 receptor blockade reverses dysmotility induced by ischemia-reperfusion in rat colon.
This study was designed to assess whether adenosine A1 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 A1 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 A1 receptor antagonists have potent therapeutic potential against ischemia-reperfusion-induced dysmotility in the colon.
Kadowaki
M
M
Pharmacological Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., 532-0031, Osaka, Japan. makotok@mail.med.upenn.edu
Tokita
K
K
Nagakura
Y
Y
Takeda
M
M
Hanaoka
K
K
Tomoi
M
M
D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D008297:Male; D058915:Purinergic P1 Receptor Antagonists; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000502:physiology; D015427:Reperfusion Injury / Q000188:drug therapy; D014970:Xanthines / Q000494:pharmacology* / Q000627:therapeutic use
C114384:FK 352; D058915:Purinergic P1 Receptor Antagonists; D011720:Pyrazoles; D011725:Pyridines; D018047:Receptors, Purinergic P1; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine