HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 296/2/G219    most recent 90485.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by de Godoy, M. A. F. Articles by Rattan, S. Search for Related Content PubMed PubMed Citation Articles by de Godoy, M. A. F. Articles by Rattan, S.

NEUROREGULATION AND MOTILITY

COX-1 vs. COX-2 as a determinant of basal tone in the internal anal sphincter

Division of Gastroenterology and Hepatology, Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Anesthesiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania

Submitted 6 August 2008 ; accepted in final form 25 November 2008

Prostanoids, produced endogenously via cyclooxygenases (COXs), have been implicated in the sustained contraction of different smooth muscles. The two major types of COXs are COX-1 and COX-2. The COX subtype involved in the basal state of the internal anal sphincter (IAS) smooth muscle tone is not known. To identify the COX subtype, we examined the effect of COX-1- and COX-2-selective inhibitors, SC-560 and rofecoxib, respectively, on basal tone in the rat IAS. We also determined the effect of selective deletion of COX-1 and COX-2 genes (COX-1^–/– and COX-2^–/– mice) on basal tone in murine IAS. Our data show that SC-560 causes significantly more efficacious and potent concentration-dependent decreases in IAS tone than rofecoxib. In support of these data, significantly higher levels of COX-1 than COX-2 mRNA were found in the IAS. In addition, higher levels of COX-1 mRNA and protein were expressed in rat IAS than rectal smooth muscle. In wild-type mice, IAS tone was decreased 41.4 ± 3.4% (mean ± SE) by SC-560 (1 x 10^–5 M) and 5.4 ± 2.2% by rofecoxib (P < 0.05, n = 5). Basal tone was 0.172 ± 0.021 mN//mg in the IAS from wild-type mice and significantly less (0.080 ± 0.015 mN/mg) in the IAS from COX-1^–/– mice (P < 0.05, n = 5). However, basal tone in COX-2^–/– mice was not significantly different from that in wild-type mice. We conclude that COX-1-related products contribute significantly to IAS tone.

smooth muscle tone; cyclooxygenase

This article has been cited by other articles:

				M. A. F. de Godoy, N. Rattan, and S. Rattan Arachidonic acid metabolites follow the preferential course of cyclooxygenase pathway for the basal tone in the internal anal sphincter Am J Physiol Gastrointest Liver Physiol, April 1, 2009; 296(4): G727 - G734. [Abstract] [Full Text] [PDF]