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Cardiovascular Research 2001 51(4):709-716; doi:10.1016/S0008-6363(01)00348-0
© 2001 by European Society of Cardiology
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Copyright © 2000, European Society of Cardiology

Accumulation of molecules involved in {alpha}1-adrenergic signal within caveolae: caveolin expression and the development of cardiac hypertrophy

Takayuki Fujitaa, Yoshiyuki Toyaa, Kousaku Iwatsuboa, Takeshi Ondaa, Kazuo Kimuraa, Satoshi Umemuraa,* and Yoshihiro Ishikawaa,b

aDepartment of Medicine and Physiology, Yokohama City University School of Medicine, Yokohama 236, Japan
bCardiovascular Research Institute, Department of Medicine, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA

* Corresponding author. Tel.: +81-45-787-2633; fax: +81-45-787-2637 umemuras{at}med.yokohama-cu.ac.jp

Objective: Caveolin, a major protein component of caveolae, is now considered to be an inhibitor of cellular growth and proliferation. In this study, we examined the localization of the molecules involved in {alpha}1-adrenergic receptor signal relative to that of caveolin in the heart and the changes in caveolin expression during the development of hypertrophy in SHR. Methods: We purified the caveolar protein fractions from rat cardiac tissues, H9C2 cells, and rat vascular smooth muscle cells. Using radioligand receptor binding assay and immunoblot analysis, we examined the distribution and the amount of {alpha}1-AR and caveolin. Results: Caveolin-3, the {alpha}1-adrenergic receptor, Gq and PLC-β ubtypes (PLC-β1, -β3) were found exclusively in the caveolar fraction in the above tissues. Caveolin-3 were co-immunoprecipitated with {alpha}1-adrenergic receptor and Gq from the cardiac tissues. The amount of caveolin subtypes expression (caveolin-1 and -3) and the amount of the {alpha}1-adrenergic receptor were examined in the hearts of SHR and age-matched WKY (4- and 24-weeks-old). The amount of caveolin-3 expression was significantly smaller in SHR at 24-weeks-old than that in SHR at 4-weeks-old and that in WKY at 24-weeks-old. Conclusions: The molecules involved in {alpha}1-adrenergic signaling are confined to the same microdomain as caveolin. A decrease in caveolin-3 expression may play a role in the development of cardiac hypertrophy in SHR, presumably through de-regulating the inhibition of growth signal in the hearts of SHR in the hypertrophic stage.

KEYWORDS Diabetes; Hypertrophy; Receptors; Signal transduction; Smooth muscle


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