Neurogenic contraction of mouse rectum via the cyclooxygenase pathway: Changes of PGE2-induced contraction with dextran sulfate sodium-induced colitis.
Recent reports suggest that cyclooxygenases (COXs) including COX-2 are constitutively expressed, and prostaglandins (PGs) regulate motility and/or contraction in the colon and rectum. This study examines the role of COXs in the regulation of neuromuscular function in longitudinal preparations of isolated rectum and distal colon (Side A, close to the transverse colon; and Side B, close to the rectum) in normal mice and after the induction of colitis by dextran sulfate sodium (DSS). In control rectum, electrical stimulation (ES)-induced contractions were inhibited by atropine and by COX inhibitors, in an independent manner. PGE(2) at 3microM caused a marked contraction, but the secondary response at 20min after the first application was 60% desensitized. In rectum from DSS-treated mice, spontaneous and ES-induced contractions were significantly less intense than in the control preparations, and the response to PGE(2) was abolished but that to 3microM acetylcholine was not. In control distal colon, the responses to PGE(2) in neither side were desensitized by the repeated application. In DSS-treated distal colon, PGE(2) response was impaired in the two regions, and was desensitized on Side B more than Side A. DSS treatment impaired contractions by 40mM KCl in rectum and on Side B but not Side A. DSS treatment increased COX-2 expression in rectum, but not in distal colon. These findings suggest that the induction of colitis by DSS affects ES- and PGE(2)-regulated motility in the order rectum>distal colon close to the rectum>distal colon in mice.
Hamada
Yuri
Y
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675, Japan.
Murakami
Ikuo
I
Kato
Erina
E
Yamane
Satoshi
S
Fujino
Hiromichi
H
Matsumoto
Kenjiro
K
Tashima
Kimihito
K
Horie
Shunji
S
Murayama
Toshihiko
T
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D003106:Colon / Q000187:drug effects / Q000201:enzymology* / Q000294:innervation / Q000503:physiopathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016264:Dextran Sulfate; D015232:Dinoprostone / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D012007:Rectum / Q000187:drug effects / Q000201:enzymology* / Q000294:innervation / Q000503:physiopathology; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D016264:Dextran Sulfate; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D000109:Acetylcholine