DOWN-REGULATION OF CAVEOLIN BY CHRONIC BETA-ADRENERGIC-RECEPTOR STIMULATION IN MICE

Caveolae, flask-shaped invaginations of cell membranes, are believed t o play pivotal roles in transmembrane transportation of molecules and cellular signaling. Caveolin, a structural component of caveolae, inte racts directly with G proteins and regulates their function. We invest igated the effect of chronic beta-adrenergic receptor stimulation on t he expression of caveolin subtypes in mouse hearts by immunoblotting a nd Northern blotting. Caveolin-1 and -3 were abundantly expressed in t he heart and skeletal muscles, but not in the brain. Continuous (-)-is oproterenol, but not (+)-isoproterenol, infusion via osmotic minipump (30 mu g.g(-1).day(-1)) for 13 days significantly downregulated both c aveolin subtypes in the heart. The expression of caveolin-1 was reduce d by 48 +/- 6.1% and that of caveolin-3 by 28 +/- 4.0% (P < 0.01, n = 8 for each). The subcellular distribution of caveolin subtypes in vent ricular myocardium was not altered as determined by sucrose gradient f ractionation. In contrast, the expression of both caveolin subtypes in skeletal muscles was not significantly changed. Our data suggest that the expression of caveolin subtypes is regulated by beta-adrenergic r eceptor stimulation in the heart.