Adenosine A1 receptor blockade reverses experimental postoperative ileus in rat colon.
Inhibition of colonic propulsive motility is the main contributor to postoperative ileus in humans. Experimental models for investigating colonic propulsion in surgically induced postoperative ileus have not previously been available. 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 the colonic motility disorder in newly developed rat experimental ileus models. When rats underwent anesthesia (pentobarbital) or surgical traumas (partial gastrectomy, cecectomy or gentle touching of the colon with fingers), colonic propulsive motility was evaluated by migration of intracolonically injected dye in awake unrestrained rats. Propulsive motility resulted in significant decrease after the treatment of the anesthesia or partial gastrectomy. Intravenous administration of either adenosine A(1) receptor antagonist reversed the slowed colonic propulsion in these experimental ileus models. The present study suggests that the blockade of adenosine A(1) receptors has therapeutic potential for postoperative ileus.
Kadowaki
Makoto
M
Pharmacological Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 532-0031, Osaka, Japan. makotok@naramed-u.ac.jp
Nagakura
Yasunori
Y
Tokita
Kenichi
K
Hanaoka
Kaori
K
Tomoi
Masaaki
M
D000758:Anesthesia; D000818:Animals; D002431:Cecostomy; D003106:Colon / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005743:Gastrectomy; D005769:Gastrointestinal Motility / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects; D007415:Intestinal Obstruction / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D011183:Postoperative Complications; D058915:Purinergic P1 Receptor Antagonists; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014970:Xanthines / Q000494:pharmacology
C114384:FK 352; D058915:Purinergic P1 Receptor Antagonists; D011720:Pyrazoles; D011725:Pyridines; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine