Neurogenic contraction of mouse rectum via the cyclooxygenase pathway: Changes of PGE(2)-induced contraction with dextran sulfate sodium-induced colitis

作者：Hamada Yuri; Murakami Ikuo; Kato Erina; Yamane Satoshi; Fujino Hiromichi; Matsumoto Kenjiro; Tashima Kimihito; Horie Shunji; Murayama Toshihiko^*

来源：Pharmacological Research, 2010, 61(1): 48-57.

DOI：10.1016/j.phrs.2009.09.001

• Mouse rectum
• Contraction
• Cyclooxygenase
• Prostaglandin
• 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 3 mu M caused a marked contraction, but the secondary response at 20 min 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 3 mu M 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 40 mM 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.

• 出版日期2010-1