Caveolin-1 gene knockout impairs nitrergic function in mouse small intestine

Authors

  • Ahmed F El-Yazbi,

    1. Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, 9-10 Medical Sciences Bldg., Edmonton, AB, Canada T6G 2H7
    Search for more papers by this author
  • Woo-Jung Cho,

    1. Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, 9-10 Medical Sciences Bldg., Edmonton, AB, Canada T6G 2H7
    Search for more papers by this author
  • Geoffrey Boddy,

    1. Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, 9-10 Medical Sciences Bldg., Edmonton, AB, Canada T6G 2H7
    Search for more papers by this author
  • Edwin E Daniel

    Corresponding author
    1. Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, 9-10 Medical Sciences Bldg., Edmonton, AB, Canada T6G 2H7
    Search for more papers by this author

Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, 9-10 Medical Sciences Bldg., Edmonton, AB, Canada T6G 2H7. E-mail: edaniel@ualberta.ca

Abstract

  • 1Caveolin-1 is a plasma membrane-associated protein that is responsible for caveolae formation. It plays an important role in the regulation of the function of different signaling molecules, among which are the different isoforms of nitric oxide synthase (NOS).
  • 2Nitric oxide (NO) is known to be an important inhibitory mediator in the mouse gut. Caveolin-1 knockout mice (Cav1−/−) were used to examine the effect of caveolin-1 absence on the NO function in the mouse small intestine (ileum and jejunum) compared to their genetic controls and BALB/c controls.
  • 3Immunohistochemical staining showed loss of caveolin-1 and NOS in the jejunal smooth muscles and myenteric plexus interstitial cells of Cajal (ICC) of Cav1−/− mice; however, nNOS immunoreactive nerves were still present in myenteric ganglia.
  • 4Under nonadrenergic noncholinergic (NANC) conditions, small intestinal tissues from Cav1−/− mice relaxed to electrical field stimulation (EFS), as did tissues from control mice. Relaxation of tissues from control mice was markedly reduced by N-omega-nitro-L-arginine (10−4 M), but relaxation of Cav1−/− animals was affected much less. Also, Cav1−/− mice tissues showed reduced relaxation responses to sodium nitroprusside (100 μM) compared to controls; yet there were no significant differences in the relaxation responses to 8-bromoguanosine-3′ : 5′-cyclic monophosphate (100 μM).
  • 5Apamin (10−6 M) significantly reduced relaxations to EFS in NANC conditions in Cav1−/− mice, but not in controls.
  • 6The data from this study suggest that caveolin-1 gene knockout causes alterations in the smooth muscles and the ICC, leading to an impaired NO function in the mouse small intestine that could possibly be compensated by apamin-sensitive inhibitory mediators.

British Journal of Pharmacology (2005) 145, 1017–1026. doi:10.1038/sj.bjp.0706289

Ancillary