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Am J Physiol Gastrointest Liver Physiol 290: G394-G403, 2006. First published September 15, 2005; doi:10.1152/ajpgi.00321.2005
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NEUROREGULATION AND MOTILITY

Impact of caveolin-1 knockout on NANC relaxation in circular muscles of the mouse small intestine compared with longitudinal muscles

Ahmed F. El-Yazbi,1 Woo Jung Cho,1 Geoffrey Boddy,1 Richard Schulz,1,2 and Edwin E. Daniel1

Departments of 1Pharmacology and 2Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada

Submitted 13 July 2005 ; accepted in final form 12 September 2005

Recently, we showed that caveolin-1 (cav1) knockout mice (Cav1–/– mice) have impaired nitric oxide (NO) function in the longitudinal muscle (LM) layer of the small intestine. The defect was a reduced responsiveness of the muscles to NO compensated by an increase in the function of apamin-sensitive, nonadrenergic, noncholinergic (NANC) mediators. In the present study, we examined similarly the effects of cav1 knockout on the relaxation in circular muscle (CM) of the mouse small intestine. CM of Cav1–/– mice also showed defective NO function, but less than in LM, as well as more activation of apamin-sensitive NANC mediators. CM of Cav1–/– mice, like LM, lacked cav1 but retained small amounts of cav3 and caveolae in the outer CM layer. In addition, we also examined the effects of a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo-[4,3-{alpha}]quinazolin-1-one (ODQ), on electric field stimulation (EFS)-mediated relaxation in both LM and CM. ODQ had an effect similar to the block of NO synthesis. Moreover, we compared the actions of two NO donors in the LM and CM of control and Cav1–/– mice. Similar to LM, CM of Cav1–/– mice showed a reduced responsiveness to the NO donors sodium nitroprusside and S-nitroso-N-acetyl penicillamine. However, both ODQ and apamin blocked the inhibitory effects of the NO donors in LM, whereas apamin had no effect in CM. In conclusion, cav1 knockout affects NO function in both LM and CM, but its effects in CM differ significantly.

caveolin-3; caveolae; nitric oxide donors; gastrointestinal tract pacing; nitric oxide; apamin



Address for reprint requests and other correspondence: E. E. Daniel, 9-10 Medical Sciences Bldg., Dept. of Pharmacology, Univ. of Alberta, Edmonton, Alberta, Canada T6G 2H (e-mail: edaniel{at}ualberta.ca)




This article has been cited by other articles:


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Am. J. Physiol. Gastrointest. Liver Physiol.Home page
A. F. El-Yazbi, W. J. Cho, R. Schulz, and E. E. Daniel
Caveolin-1 knockout alters beta-adrenoceptors function in mouse small intestine
Am J Physiol Gastrointest Liver Physiol, December 1, 2006; 291(6): G1020 - G1030.
[Abstract] [Full Text] [PDF]




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